Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study.

OBJECTIVE: To identify the effective predictors for therapeutic outcomes based on intermittent theta-burst stimulation (iTBS). DESIGN: A sham-controlled, double-blind parallel study design. SETTING: A tertiary hospital. PARTICIPANTS: People with stroke (N=72) who presented with unilateral hemiplegia. INTERVENTIONS: Ten consecutive sessions of real or sham iTBS were implemented with the aim of enhancing hand function. Patients were categorized into 4 groups according to the presence (MEP+) or absence (MEP-) of motor-evoked potentials (MEPs) and grip strength according to the Medical Research Council (MRC) scale. MAIN OUTCOME MEASURES: Cortical excitability, Wolf Motor Function Test (WMFT), finger-tapping task (FT), and simple reaction time were performed before and after the sessions. RESULTS: MEPs and the MRC scale were predictive of iTBS therapeutic outcomes. Group A (MEP+, MRC>1) exhibited the greatest WMFT change (7.6±2.3, P<.001), followed by group B (MEP-, MRC>1; 5.2±2.2 score change) and group C (MEP-, MRC=0; 2.3±1.5 score change). These improvements were correlated significantly with baseline motor function and ipsilesional maximum MEP amplitude. CONCLUSIONS: The effectiveness of iTBS modulation for poststroke motor enhancement depends on baseline hand grip strength and the presence of MEPs. Our findings indicate that establishing neurostimulation strategies based on the proposed electrophysiological and clinical criteria can allow iTBS to be executed with substantial precision. Effective neuromodulatory strategies can be formulated by using electrophysiological features and clinical presentation information as guidelines.

Efficacy of synchronous verbal training during repetitive transcranial magnetic stimulation in patients with chronic aphasia.

BACKGROUND AND PURPOSE: Although multiple studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may facilitate recovery after stroke, the efficacy of synchronous speech therapy integrated with an rTMS protocol has yet to be determined. We investigated language responses to this strategy and determined the longevity of the resulting therapeutic outcomes. METHODS: Forty-five patients with stroke who presented with nonfluent aphasia were randomly assigned to the TMSsyn group and underwent synchronous picture-naming training together with contralesional 1 Hz-rTMS for 10 daily sessions. The TMSsub group underwent subsequent picture-naming activity after the primed 1 Hz-rTMS, and the TMSsham group received concurrent naming task along with the sham 1 Hz-rTMS. The Concise Chinese Aphasia test and the picture-naming test were performed before, immediately, and after 3 months of the intervention. RESULTS: TMSsyn showed significantly superior results in Concise Chinese Aphasia test score (P<0.001), expression and description subtests (P<0.001), and action (P=0.02) and object naming activity (P=0.008); the superior results lasted for 3 months (P=0.005), in comparison with the TMSsub and TMSsham groups. CONCLUSIONS: We established a real-time model that involved implementing verbal tasks together with the rTMS protocol. Our results confirmed that the strategy yielded favorable outcomes that were of considerable longevity. The results also indicated that the rTMS protocol and language training can be combined to achieve outcomes superior to those obtained when used separately. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02120508.

Long-term sacral magnetic stimulation for refractory stress urinary incontinence.

OBJECTIVE: To evaluate the effects of sacral magnetic stimulation (SMS) on functional and urodynamic improvement in patients with refractory stress urinary incontinence (SUI). DESIGN: A sham-controlled, double-blind, parallel study design with a 4.5-month follow-up. SETTING: A tertiary hospital. PARTICIPANTS: Women (age, 45-75y) with SUI refractory to first-line management (N=34) were allocated to either an experimental (n=20) group or a sham (n=14) group. INTERVENTIONS: The SMS protocol consisted of 5-Hz, 20-minute treatments administered over the bilateral third sacral roots, with the intensity set at approximately 70% of the maximal output, for 12 consecutive weekdays. MAIN OUTCOME MEASURES: Urodynamic assessments and 2 life stress questionnaires, namely, the Urge-Urinary Distress Inventory (U-UDI) and the Overactive Bladder Questionnaire (OAB-q), were administered pre- and post-SMS intervention. We administered the U-UDI (primary outcome measure) and the OAB-q at 3-week intervals during the follow-up period until 18 weeks after the final intervention. RESULTS: The experimental group exhibited significant improvements in both U-UDI and OAB-q scores postintervention (P=.011-.014) and at follow-up visits (P<.001-.007) compared with the sham group. In addition, significant increases in bladder capacity, urethral functional length, and the pressure transmission ratio (P=.009-.033) were noted postintervention. Multivariate regression analysis revealed that patients with more severe symptoms benefited more from SMS. A poorer baseline U-UDI score and a shorter urethral functional length were associated with a greater response to SMS. CONCLUSIONS: Our observations of a greater response to SMS in patients with more severe SUI than in those with mild symptoms, as well as the long-term benefits of the treatment, confirm the efficacy of SMS in treating SUI.

Efficacy of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation to enhance motor recovery in hemiplegic stroke patients.

BACKGROUND AND PURPOSE: Although there has been extensive research on the effectiveness of repetitive transcranial magnetic stimulation (rTMS) to improve patients' motor performance after experiencing chronic stroke, explicit findings on the coupling of different rTMS protocols are meager. We designed this sham-controlled randomized study to investigate the potential for a consecutive suppressive-facilitatory TMS protocol to improve motor outcomes after chronic stroke. METHODS: Fifty-four chronic hemiplegic stroke patients were allocated across 4 groups to undergo 20 daily sessions of (1) 1 Hz rTMS over the contralesional primary motor cortex (M1) and then intermittent theta burst stimulation over the ipsilesional M1 (group A); (2) contralesional sham stimulation and then ipsilesional real intermittent theta burst stimulation (group B); (3) contralesional real 1 Hz rTMS and then ipsilesional sham stimulation (group C); or (4) bilateral sham-control procedures (group D). We tested cortical excitability and motor activity assessments at the baseline, postpriming rTMS, and postconsequent rTMS periods. RESULTS: At post, group A showed greater muscle strength, Fugl-Meyer Assessment (FMA), Wolf Motor Function test, and reaction time improvement in comparison with group B (P<0.001≈0.003) and group C (P=0.001≈0.003). Correlation analyses in group A revealed a close relation between contralesional map area decrement and Wolf Motor Function test gain (P=0.005; r=-0.75), and also revealed ipsilesional map area increment and reaction time decrement (P=0.02; r=-0.87). We detected no such relations in the other 3 groups. CONCLUSIONS: Our clinical trials established an extended timeframe during which conditioning could be safely continued and produced more favorable outcomes in facilitating motor performance and ameliorating interhemispheric imbalance than those obtained from single-course rTMS modulation alone.

Concordance and discrepancy between electrodiagnosis and magnetic resonance imaging in cervical root avulsion injuries.

To clarify the relationships between electromyography (EMG) and magnetic resonance imaging (MRI), we compared findings in 37 selected patients who presented with cervical root avulsion injuries. Nerve root repair with C4-T1 hemilaminectomy was subsequently performed on 19 patients. The agreement between the two evaluative modalities with complete or incomplete lesions of ventral root and pre- or postganglionic lesions of dorsal root was measured for each root level. Both with ventral and dorsal root evaluation, C6, C7, and C8 yielded high agreement values, ranging from 86% to 94%. C5 manifested the lowest agreement values: 54% on ventral root assessment. Additionally, EMG, in comparison with MRI, revealed a higher quantity of implicated injured components. MRI, in turn, detected more lesion components than surgical exploration alone achieved. The capability of EMG to recognize axonotmesis leads to the discrepant findings between the two modalities. The visualization of mild neurotmesis by MRI, which cannot be achieved by surgical inspection, results in divergent findings between the two modalities. Both EMG and the MRI play crucial roles in preoperative assessment, and they may complement each other.

Differential effect of conditioning sequences in coupling inhibitory/facilitatory repetitive transcranial magnetic stimulation for poststroke motor recovery.

INTRODUCTION: While neuromodulation through unihemispheric repetitive transcranial magnetic stimulation (rTMS) has shown promise for the motor recovery of stroke patients, the effectiveness of the coupling of different rTMS protocols remains unclear. AIMS: We aimed to test the long-term efficacy of this strategy with different applying sequences and to identify the electrophysiological correlates of motor improvements to the paretic hand. RESULTS: In our sham-controlled, double-blinded parallel study, 48 stroke patients (2-6 months poststroke) were randomly allocated to three groups. Group A underwent 20-session rTMS conditioning initiated with 10-session 1 Hz rTMS over the contralesional primary motor cortex (M1), followed by 10-session intermittent theta burst stimulation (iTBS) consequently over the ipsilesional M1; Group B underwent the same two paradigms but in reverse; and Group C received sham stimulation that was identical to Group A. We tested cortical excitability and motor assessments at the baseline, postpriming rTMS, postconsequent rTMS, and at 3-months follow-up. Group A manifested greater improvement than Group B in Fugl-Meyer Assessment (FMA), Wolf Motor Function testing (WMFT) score, and muscle strength (P = 0.001-0.02) post the priming rTMS. After the consequent rTMS, Group A continued to present a superior outcome than Group B in FMA (P = 0.015) and WMFT score (P = 0.008) with significant behavior-electrophysiological correlation. CONCLUSIONS: Conditioning the contralesional M1 prior to ipsilesional iTBS was found to be optimal for enhancing hand function, and this effect persisted for at least 3 months. Early modulation within 6 months poststroke rebalances interhemispheric competition and appears to be a feasible time window for rTMS intervention.

The persistent and broadly modulating effect of inhibitory rTMS in nonfluent aphasic patients: a sham-controlled, double-blind study.

BACKGROUND: While prior preliminary studies have broadened our understanding of how repetitive transcranial magnetic stimulation (rTMS) improves language outcomes in stroke patients with nonfluent aphasia, the evidence base of the effectiveness of this method remains inadequate. OBJECTIVE: In this study, we aimed to strengthen the evidence that this approach improves language performance and to identify characteristics of patients predisposed to benefit most from this treatment. METHODS: Fifty-six stroke patients with nonfluent aphasia were randomly allocated to a real or a sham stimulation group: Group A (n = 33), who underwent 10 sessions of 1-Hz rTMS over the contralesional pars triangularis (PTr), and Group B (n = 23), who received sham 1-Hz stimulation. We performed the Picture Naming Test and the Concise Chinese Aphasia Test (CCAT) at the baseline, post-rTMS intervention, and at 3-month follow-up. RESULTS: Group A showed significantly greater improvement than Group B in CCAT scoring (P < .001), object-naming accuracy (P = .01), and naming reaction time (P = .004). The CCAT scoring and naming testing changes for Group A were persistent at 3 months following intervention (P = .008). Patients who had a lower contralesional rest motor threshold (rMT) were predisposed to a favorable therapeutic outcome (P = .006), independent of aphasia type, severity, and duration. CONCLUSIONS: The results of this study provide evidence that inhibitory rTMS, through downregulating the circuitry of the right pars triangularis (PTr), achieves a persistent and broadly modulating effect, irrespective of aphasia severity and subtype. Patients who show lower rMT in the right motor system would seem to benefit the most from inhibitory rTMS.

Inhibitory repetitive transcranial magnetic stimulation of the contralesional premotor and primary motor cortices facilitate poststroke motor recovery.

PURPOSE: The premotor cortex plays a major role in motor planning and control, exhibiting hierarchical importance comparable to that of the primary motor cortex (M1). In this study, we compared the effects of cPMd modulation, which was achieved using inhibitory repetitive transcranial magnetic stimulation (rTMS), with those of contralesional M1 (cM1) modulation, to elucidate the roles of both regions on longitudinal motor recovery following a stroke. METHODS: Forty-four patients who had sustained hemiplegia for 3 to 12 months were randomly allocated to a cPMd group, cM1 group, or sham group and received 10 sessions of 1-Hz rTMS. The Medical Research Council (MRC) Scale, Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), and a cortical excitability test were administered pre- and post- rTMS intervention. RESULTS: cPMd modulation yielded significant improvements in MRC, FMA, and WMFT scores compared with sham stimulation and a significant effect on cortical excitability suppression equivalent to that of cM1 modulation, but engendered effects on motor improvement inferior to those of cM1 modulation. CONCLUSIONS: In patients with chronic stroke, the cPMd can fulfill a role similar to that of the cM1 in interhemispheric imbalance, which can be ameliorated by applying inhibitory rTMS to achieve substantial motor restoration.

Efficacy of spinal magnetic stimulation in elderly persons with chronic constipation.

BACKGROUND: The development of primary constipation in elderly adults usually has a multifactorial etiology. Slow transit constipation and pelvic floor dysfunction (PFD) are the two most commonly seen constipation subtypes in the elderly. PFD is usually a persistent condition that remains unresponsive to treatment in spite of various therapies currently available to relieve constipation. The aim of this study was to assess the usefulness of spinal magnetic stimulation (SMS) in controlling intractable constipation in elderly patients. METHODS: Nineteen patients over the age of 65 with intractable constipation were enrolled in this study, and participated in a 12-session magnetic conditioning protocol consisting of a 20-minute stimulation session once daily. Colonic transit time (CTT) and the dynamics of evaluation as revealed in defecography were measured, and the Knowles-Eccersley-Scott Symptom (KESS) Questionnaire was administered before the intervention, and after finishing the protocol. RESULTS: There was a statistically significant improvement in CTT and defecography following the intervention. The difference in the anorectal angles between resting and evacuation (p = 0.001) and the changes in pelvic floor descent (p = 0.011) both reached significance after the intervention. The mean CTT (p = 0.001), Knowles-Eccersley-Scott Symptom score (p = 0.001), frequency of bowel movement (p = 0.005), unsuccessful evacuation (p = 0.018), and time needed for bowel hygiene (p = 0.032) all showed marked improvement after SMS conditioning. CONCLUSION: Our findings reveal that SMS intervention may benefit elderly patients with severe constipation. The amelioration of geriatric bowel dysfunction across the subtypes of slow transit constipation and PFD indicated that SMS, featuring broad-spectrum applications, can be an effective form of adjuvant treatment in the care of elderly adults.

Efficacy of functional magnetic stimulation in neurogenic bowel dysfunction after spinal cord injury.

OBJECTIVE: The aims of this study were to assess the usefulness of functional magnetic stimulation in controlling neurogenic bowel dysfunction in spinal cord injured patients with supraconal and conal/caudal lesions, and to investigate the efficacy of this regimen with a 3-month follow-up. DESIGN: A longitudinal, prospective before-after trial. SUBJECTS: A total of 22 patients with chronic spinal cord injured and intractable neurogenic bowel dysfunction. They were divided into group 1 (supraconal lesion) and group 2 (conal/caudal lesion). METHODS: The colonic transit time assessment and Knowles-Eccersley-Scott Symptom Questionnaire were carried out for each patient before they received a 3-week functional magnetic stimulation protocol and on the day following the treatment. RESULTS AND CONCLUSION: Following functional magnetic stimulation, the mean colonic transit time for all patients decreased from 62.6 to 50.4 h (p<0.001). The patients' Knowles-Eccersley-Scott Symptom scores decreased from 24.5 to 19.2 points (p<0.001). The colonic transit time decrement in both group 1 (p=0.003) and group 2 (p=0.043) showed significant differences, as did the Knowles-Eccersley-Scott Symptom score in both groups following stimulation and in the 3-month follow-up results (p<0.01). The improvements in bowel function indicate that functional magnetic stimulation,featuring broad-spectrum application, can be incorporated successfully into other therapies as an optimal adjuvant treatment for neurogenic bowel dysfunction resulting from spinal cord injury.

Functional magnetic stimulation in constipation associated with Parkinson's disease.

OBJECTIVE: The aims of this study were: (i) to investigate the effect of functional magnetic stimulation on total colonic transit time in patients with Parkinson's disease; (ii) to compare the changes in dynamic recto-anal behaviour during filling and defaecation in response to this regimen; and (iii) to study the carry-over effects with a 3-month follow-up. DESIGN: A longitudinal, prospective before-after trial. SUBJECTS: Sixteen patients with Parkinson's disease enrolled in this study. No subject withdrew from the study as a result of serious adverse events. METHODS: A 3-week magnetic conditioning protocol, consisting of a 20-min stimulation session twice daily. Colonic transit time, Knowles-Eccersley-Scott Symptom Questionnaire and the dynamics of defecography were carried out before the intervention and on the final day of the protocol. RESULTS AND CONCLUSION: There was a statistically significant reduction in colonic transit time and in the questionnaire score following the intervention. The difference in the anorectal angles between resting and evacuating process and the changes in pelvic floor descent all reached significance after the intervention. The therapeutic effects that achieved significance remained constant in the 3-month follow-up result. Functional magnetic stimulation may facilitate colonic motility in Parkinson's disease and straighten the anorectal angle, allowing smooth access of rectal contents to the anal canal.

Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor.

The human testicular receptor 4 (TR4) shares structural homology with members of the nuclear receptor superfamily. Some other members of this superfamily were able to regulate the transcriptional activity of the human oxytocin (OXT) promoter by binding to the first DR0 regulatory site. However, little investigation was conducted systematically in the study of the second dDR4 site of OXT proximal promoter, and the relationship between the first and the second sites of OXT promoter. Here, we demonstrated for the first time that TR4 could increase the proximal promoter activity of the human OXT gene via DR0, dDR4, and OXT (both DR0 and dDR4) elements, respectively. TR4 might induce OXT gene expression through the OXT element in a dose-dependent manner. However, there is no synergistic effect between DR0 and dDR4 elements during TR4 transactivation. Taken together, these results suggested that TR4 should be one of important regulators of OXT gene expression.