Kwong-Kum Liao

Effects of Repetitive Transcranial Magnetic Stimulation on Motor Functions in Patients With Stroke: A Meta-Analysis

Background and Purpose— The purpose of this study was to perform a meta-analysis of studies that investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function in patients with stroke. Methods— We searched for randomized controlled trials published between January 1990 and October 2011 in PubMed, Medline, Cochrane, and CINAHL using the following key words: stroke, cerebrovascular accident, and repetitive transcranial magnetic stimulation. The mean effect size and a 95% CI were estimated for the motor outcome and motor threshold using fixed and random effect models. Results— Eighteen of the 34 candidate articles were included in this analysis. The selected studies involved a total of 392 patients. A significant effect size of 0.55 was found for motor outcome (95% CI, 0.37–0.72). Further subgroup analyses demonstrated more prominent effects for subcortical stroke (mean effect size, 0.73; 95% CI, 0.44–1.02) or studies applying low-frequency rTMS (mean effect size, 0.69; 95% CI, 0.42–0.95). Only 4 patients of the 18 articles included in this analysis reported adverse effects from rTMS. Conclusions— rTMS has a positive effect on motor recovery in patients with stroke, especially for those with subcortical stroke. Low-frequency rTMS over the unaffected hemisphere may be more beneficial than high-frequency rTMS over the affected hemisphere. Recent limited data suggest that intermittent theta-burst stimulation over the affected hemisphere might be a useful intervention. Further well-designed studies in a larger population are required to better elucidate the differential roles of various rTMS protocols in stroke treatment.

Gait Training—Induced Change in Corticomotor Excitability in Patients With Chronic Stroke

Background. Numerous studies have reported the effects of gait training on motor performance after stroke. However, there is limited information on treatment-induced changes in corticomotor excitability. Objectives. The purpose of the study was to investigate the effects of additional gait training on motor performance and corticomotor excitability and to demonstrate the relationship between motor improvement and corticomotor excitability change in patients with chronic stroke. Methods. Fourteen patients were randomly assigned to the experimental or control group. Participants in both groups participated in general physical therapy. Those in the experimental group received additional body weight− supported treadmill training for 4 weeks. All participants received baseline and posttreatment assessments. The outcome measures included assessment of the Berg Balance Scale (BBS) and gait parameters. Focal transcranial magnetic stimulation was used to measure the motor threshold, map size, and location of the amplitude-weighted center of gravity of the motor map for the tibialis anterior (TA) and abductor hallucis (AH) muscles. Results . After general physical therapy, we noted that the patients showed an improvement only in walking speed and cadence, and there were no significant changes in corticomotor excitability. After additional gait training, participants improved significantly on BBS score, walking speed, and step length. Moreover, the motor threshold for TA decreased significantly in the unaffected hemisphere. The map size for TA was increased in both hemispheres, whereas that for AH was increased only in the affected hemisphere. There were significant differences between the change scores of the groups in terms of walking speed, step length, and motor threshold for TA in the unaffected hemisphere and map size for AH in the affected hemisphere. Additionally, the changes in corticomotor excitability correlated with functional improvement. Conclusions . Additional gait training may improve balance and gait performance and may induce changes in corticomotor excitability.

Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism

A genetic analysis identified 2 patients, approximately one‐tenth of our patients with familial parkinsonism, who had expanded trinucleotide repeats in SCA2 genes. The reduction of 18F‐dopa distribution in both the putamen and caudate nuclei confirmed that the nigrostriatal dopaminergic system was involved in parkinsonian patients with SCA2 mutation.

rTMS Combined With Task-Oriented Training to Improve Symmetry of Interhemispheric Corticomotor Excitability and Gait Performance After Stroke: A Randomized Trial

Background. The model of interhemispheric competition after stroke has been established for the upper but not for the lower extremity. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Objective. The purpose of this study was to investigate the effects of rTMS followed by task-oriented training on cortical excitability and walking performance in individuals with chronic stroke. Methods. A total of 24 patients with average Fugl-Meyer lower limb scores of 17.88 ± 5.27 and average walking speeds of 63.81 ± 18.25 cm/s were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by task-oriented training (30 minutes) for 10 sessions over 2 weeks. Repetitive TMS was applied at a 1-Hz frequency over the leg area of the motor cortex of the unaffected hemisphere for 10 minutes. Outcomes, including motor-evoked potential (MEP), lower-extremity Fugl-Meyer score, and gait performance, were measured before and after training. Results. Decreased interhemispheric asymmetry of the amplitude of the MEP was noted after rTMS and task-oriented training. Improvement in spatial asymmetry of gait was comparable with increased symmetry in interhemispheric excitability. Motor control and walking ability were also significantly improved after rTMS and task-oriented training. Conclusions. rTMS enhances the effect of task-oriented training in those with chronic stroke, especially by increasing gait spatial symmetry and corticomotor excitability symmetry.

PRRT2 Mutations in Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions in a Taiwanese Cohort

Background Mutations in the PRRT2 gene have recently been identified in patients with familial paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and patients with sporadic PKD/IC from several ethnic groups. To extend these recent genetic reports, we investigated the frequency and identities of PRRT2 mutations in a cohort of Taiwanese patients with PKD/IC. Methodology and Principal Findings We screened all 3 coding exons of PRRT2 for mutations in 28 Taiwanese patients with PKD/IC. Among them, 13 had familial PKD/IC and 15 were apparently sporadic cases. In total, 7 disparate mutations were identified in 13 patients, including 8 familial cases and 5 apparently sporadic cases. The mutations were not present in 500 healthy controls. Four mutations were novel. One patient had a missense mutation and all other patients carried PRRT2 mutations putatively resulting in a protein truncation. Haplotype analysis revealed that 5 of the 7 patients with the PRRT2 p.R217Pfs*8 mutation shared the same haplotype linked to the mutation. Conclusions and Significance PRRT2 mutations account for 61.5% (8 out of 13) of familial PKD/IC and 33.3% (5 out of 15) of apparently sporadic PKD/IC in the Taiwanese cohort. Most patients with the PRRT2 p.R217Pfs*8 mutation in Taiwan likely descend from a single common ancestor. This study expands the spectrum of PKD/IC-associated PRRT2 mutations, highlights the pathogenic role of PRRT2 mutations in PKD/IC, and suggests genetic heterogeneity within idiopathic PKD.

Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis

PURPOSE To evaluate the antiepileptic efficacy of low frequency repetitive transcranial magnetic stimulation (rTMS) in medically intractable epilepsy. METHODS A comprehensive literature search was performed on articles published from 1990 to 2010 in Medline, Pubmed, CINAHL, and Cochrane using the following keywords: epilepsy, seizure, transcranial magnetic stimulation, repetitive transcranial magnetic stimulation. Two reviewers assessed article eligibility and extracted the data independently. For outcome measures, effect size and 95% confidence interval (CI) were calculated for seizure frequency, spike number, duration of epileptiform abnormalities (EAs), and resting motor threshold (RMT) by using fixed and random effect models. RESULTS Eleven articles were identified, with a total of 164 participants. Based on seizure frequency, a significant effect size was found (effect size: 0.34, with a 95% CI at 0.10-0.57). Considering between-study heterogeneity, we conducted a second meta-analysis, and the underlying etiology was considered important for the treatment effect. Cortical dysplasia or neocortical epilepsy showed an effect size of 0.71, with a 95% CI at 0.30-1.12. In contrast, other epileptic disorders showed an effect size of 0.22. CONCLUSION Low frequency rTMS has a favorable effect on seizure reduction, particularly evident in patients with neocortical epilepsy or cortical dysplasia.

Combination of rTMS and Treadmill Training Modulates Corticomotor Inhibition and Improves Walking in Parkinson Disease A Randomized Trial

Background. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Combinations of rehabilitation therapies with rTMS might enhance the therapeutic effects. Objective. The purpose of this study was to investigate the effects of high-frequency rTMS followed by treadmill training on cortical inhibition and walking function in individuals with Parkinson disease (PD). Methods. A total of 20 patients with PD were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by treadmill training (30 minutes) for 12 sessions over 4 weeks. Repetitive TMS was applied at a 5-Hz frequency over the leg area of the motor cortex contralaterally to the more affected side for 6 minutes. Outcomes, including corticomotor inhibition and walking performance, were measured before and after training. Results. The results showed significant time effects on almost all corticomotor and functional variables. There are significant interaction effects between group and time of evaluation on the motor threshold, duration of the cortical silent period, and short interval intracortical inhibition of the contralateral hemisphere relatively to the more affected side as well as on the fast walking speed and timed up and go. Conclusions. The findings suggested that combination of rTMS and treadmill training enhances the effect of treadmill training on modulation of corticomotor inhibition and improvement of walking performance in those with PD.

Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: clinical implications.

Among 242 patients with apparently sporadic Parkinsons disease, a 70‐year‐old man with a CAG repeat number of 37 in the SCA2 gene was identified. He has remained responsive to levodopa 14 years after onset and has had no overt signs suggesting cerebellar dysfunction. Although it is not possible to confirm if this patient has a de novo mutation of the SCA2 gene, this genetic defect seems to be contributing to his parkinsonian features and further supports the concept that apparently sporadic, late‐onset, levodopa‐responsive Parkinsons disease may have multiple causes.

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: A pilot study

BACKGROUND We demonstrated that prolonged transcranial magnetic intermittent theta burst stimulation (iTBS, 1200 pulses/session=iTBS1200) produces longer-lasting facilitation in corticospinal excitability than ordinary form of iTBS in healthy subjects. OBJECTIVE Here we show the safety and small-scale efficacy of iTBS1200 over ipsilesional primary motor cortex (M1) in subacute stroke patients. METHODS Twelve patients with first-time, subacute ischemic stroke of the middle cerebral artery were randomized into two groups that received 10 daily-sessions of either iTBS1200 or sham stimulation (n=6/group) over ipsilesional M1 hand region in addition to medical and rehabilitation treatments. The primary outcome measures were safety and tolerability. The secondary outcome measures included the National Institute of Health Stroke Scale (NIHSS), Upper Extremity Fugl-Meyer Test (UE-FMT), Action Research Arm Test (ARAT), active motor thresholds (aMTs)/motor-evoked potentials (MEPs) from the extensor carpi radialis (ECR), and magnetoencephalography on post-intervention day 1 and post-stroke day 60. RESULTS iTBS or sham stimulation was well tolerated by all patients without seizures or significant adverse effects. Compared with the matched controls, the iTBS group showed measurable improvements in the NIHSS and the proximal UE-FMT scores on post-intervention day 1 and post-stroke day 60. Nevertheless, the hand ARAT scores, aMT and MEPs from the paretic ECR were not different between groups. Post-movement beta synchronization increased over iTBS-conditioned M1 on post-intervention day 1 in testable patients. CONCLUSIONS Repetitive sessions of iTBS1200 over ipsilesional M1 of subacute stroke patients are safe and the potential benefits encourage a larger trial to determine the efficacy in stroke patients. (ClinicalTrials.gov: NCT-01323881).

Cortico-cortical phase synchrony in auditory mismatch processing

Previous studies have shown a reduced MMN in patients with lesions in the temporal or frontal lobes, suggesting a temporal-frontal involvement in change detection. However, how the temporal lobe interacts with other brain areas in responding to unexpected deviant stimuli remains unclear. This study aimed to evaluate the functional connectivity between cerebral regions by measuring the phase synchrony of magnetoencephalographic (MEG) signals elicited by regular simple tones and their duration-deviants in an oddball paradigm. We measured MEG responses to deviant (1000-Hz frequency, 50-ms duration, probability of 15%) and standard (1000-Hz frequency, 100-ms duration) sounds in 10 healthy adults. By using the Morlet wavelet-based analysis, relative phase synchronization values of 4-40 Hz MEG responses at 150-300 ms after stimulus onset were calculated with respect to a reference channel from the temporal region. Phase synchronization was clearly identified between the temporal and ipsilateral frontal region in the auditory evoked responses. This temporal-frontal synchronization was significantly larger in deviants-elicited than standards-elicited activation at 4-25 Hz in the left hemisphere (p<0.05), and at 4-8 Hz in the right hemisphere (p<0.01). Also, temporal-temporal and temporal-parietal phase synchronies were found in deviants-evoked 4-8 Hz responses. The present results suggest an involvement of temporal-temporal, temporal-frontal, and temporal-parietal neuronal network in detecting auditory change. Phase synchronization analysis may provide a useful window to further understanding of the cerebral reactivity during the processing of auditory deviants.