A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.

Laboratory and febrile features after joint surgery in patients with rheumatoid arthritis treated with tocilizumab.

OBJECTIVES: To understand the acute phase responses to surgical intervention in patients with rheumatoid arthritis (RA) treated with the anti-interleukin (IL)6 receptor antibody, tocilizumab. METHODS: In a retrospective 1:1 pair-matched case-control study, 22 tocilizumab-treated RA cases and 22 cases treated with conventional disease-modifying antirheumatic drugs (DMARDs) and matched for type of surgery, age and sex were evaluated for body temperature every day, and blood C-reactive protein (CRP) levels and white blood cell (WBC), neutrophil and lymphocyte counts on days -1, 1, 3 and weeks 1 and 2 after joint surgery. Safety issues were also monitored. RESULTS: No complications of infection or delay of wound healing occurred in either patient group. Tocilizumab partially, but significantly, suppressed the increase in body temperature on postoperative days 1 and 2, compared with DMARDs (average (SD) maximum increase in temperature was 0.45 (0.1) degrees C in the tocilizumab group and 0.78 (0.1) degrees C in the DMARD group; p<0.01). Tocilizumab completely suppressed the increase in CRP after surgery, whereas all cases treated with DMARDs showed a significant increase of CRP at postoperative day 1 (5.5 (0.6) mg/dl; p<0.001). WBC, neutrophil and lymphocyte counts showed no remarkable change after surgery, and there was no significant difference in any cell counts between the patient groups. CONCLUSIONS: Within this small number of cases, safe operations on patients were performed during tocilizumab treatment. Tocilizumab suppressed fever and increase of CRP after surgery, whereas there was no influence on the transition in number of leukocytes. This characteristic postoperative response should be considered during tocilizumab treatment.

Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA microarray analysis.

OBJECTIVES: Systemic juvenile idiopathic arthritis (sJIA) is a rheumatic disease in childhood characterised by systemic symptoms and a relatively poor prognosis. Peripheral leukocytes are thought to play a pathological role in sJIA although the exact cause of the disease is still obscure. In this study, we aimed to clarify cellular functional abnormalities in sJIA. METHODS: We analysed the gene expression profile in peripheral leukocytes from 51 patients with sJIA, 6 patients with polyarticular type JIA (polyJIA) and 8 healthy children utilising DNA microarrays. Gene ontology analysis and network analysis were performed on the genes differentially expressed in sJIA to clarify the cellular functional abnormalities. RESULT: A total of 3491 genes were differentially expressed in patients with sJIA compared to healthy individuals. They were functionally categorised mainly into a defence response group and a metabolism group according to gene ontology, suggesting the possible abnormalities in these functions. In the defence response group, molecules predominantly constituting interferon (IFN)gamma and tumour necrosis factor (TNF) network cascades were upregulated. In the metabolism group, oxidative phosphorylation-related genes were downregulated, suggesting a mitochondrial disorder. Expression of mitochondrial DNA-encoded genes including cytochrome c oxidase subunit 1(MT-CO1) and MT-CO2 were suppressed in patients with sJIA but not in patients with polyJIA or healthy children. However, nuclear DNA-encoded cytochrome c oxidases were intact. CONCLUSION: Our findings suggest that sJIA is not only an immunological disease but also a metabolic disease involving mitochondria disorder.

In situ transmission electron microscopy observation of the growth of bismuth oxide whiskers.

Growth of bismuth oxide (most probably Bi2O3) was observed in situ in a transmission electron microscope. Bi liquid particles were dispersed on the substrates of diamond or SiO2. Introduction of oxygen up to 5 x 10-4 Pa resulted in formation of bismuth oxide (most probably Bi2O3) whiskers. The growth mechanism of the whisker was discussed in terms of a vapor-liquid-solid (VLS) mechanism. It is suggested that the liquid droplet of Bi acts as a physical catalyst for growth of bismuth oxide (most probably Bi2O3) whiskers.

Neural correlates of regional EEG power change.

To clarify the physiological significance of task-related change of the regional electroencephalogram (EEG) rhythm, we quantitatively evaluated the correlation between regional cerebral blood flow (rCBF) and EEG power. Eight subjects underwent H2 15O positron emission tomography scans simultaneously with EEG recording during the following tasks: rest condition with eyes closed and open, self-paced movements of the right and left thumb and right ankle. EEG signals were recorded from the occipital and bilateral sensorimotor areas. Cortical activation associated with EEG rhythm generation was studied by the correlation between rCBF and EEG power. There were significant negative correlations between the sensorimotor EEG rhythm at 10-20 Hz on each side and the ipsilateral sensorimotor rCBF and between the occipital EEG rhythm at 10-20 Hz and the occipital rCBF. The occipital EEG rhythm showed a positive correlation with the bilateral medial prefrontal rCBF, while the right sensorimotor EEG rhythm showed a positive correlation with the left prefrontal rCBF. In conclusion, decrease in the regional EEG rhythm at 10-20 Hz might represent the neuronal activation of the cortex underlying the electrodes, at least for the visual and sensorimotor areas. The neural network including the prefrontal cortex could play an important role to generate the EEG rhythm.

Dominance of ipsilateral corticospinal pathway in congenital mirror movements.

OBJECTIVE: To clarify the mechanism of congenital mirror movements. DESIGN: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. RESULTS: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. CONCLUSIONS: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex.

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.

Increased synchronization of cortical oscillatory activities between human supplementary motor and primary sensorimotor areas during voluntary movements.

In human, both primary and nonprimary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas has not been fully clarified yet. Because it has been proposed that the functional coupling among cortical areas might be achieved by the synchronization of oscillatory activity, we investigated the electrocorticographic coherence between the supplementary motor and primary sensorimotor areas (SMA and S1-M1) by means of event-related partial coherence analysis in 11 intractable epilepsy patients. We found premovement increase of coherence between the SMA proper and S1-M1 at the frequency of 0-33 Hz and between the pre-SMA and S1-M1 at 0-18 Hz. Coherence between the SMA proper and M1 started to increase 0.9 sec before the movement onset and peaked 0.3 sec after the movement. There was no systematic difference within the SMA (SMA proper vs pre-SMA) or within the S1-M1, in terms of the time course as well as the peak value of coherence. The phase spectra revealed near-zero phase difference in 57% (20 of 35) of region pairs analyzed, and the remaining pairs showed inconsistent results. This increase of synchronization between multiple motor areas in the preparation and execution of voluntary movements may reflect the multiregional functional interactions in human motor behavior.

Coherence between cortical and muscular activities after subcortical stroke.

BACKGROUND AND PURPOSE: Functional connection between the motor cortex and muscle can be measured by electroencephalogram-electromyogram (EEG-EMG) coherence. To evaluate the functional connection to muscle between contralateral and ipsilateral motor cortices after pyramidal tract lesions, we investigated 6 patients with chronic subcortical stroke. METHODS: High-resolution EEG and EMG of the hand, forearm, and biceps muscles were recorded during 3 tonic contraction tasks: (1) elbow flexion, (2) wrist extension, and (3) power grip. To evaluate the cortical control of EMG, EEG-EMG coherence was computed. RESULTS: EEG-EMG coherence was localized over the contralateral sensorimotor area in all circumstances, and there was no significant coherence at the ipsilateral side. EEG-EMG coherence was significantly smaller on the affected side for the hand and forearm muscles but not for the biceps muscle. CONCLUSIONS: All direct functional connections to muscle after recovered subcortical stroke come from the contralateral motor cortex. The different effects of the lesion on the proximal and distal muscles appear to be associated with the strength of the corticospinal pathway.

Construction of a series of mutants lacking all of the four major mex operons for multidrug efflux pumps or possessing each one of the operons from Pseudomonas aeruginosa PAO1: MexCD-OprJ is an inducible pump.

We constructed a series of deletion mutants lacking all of the four major mex operons for Mex multidrug efflux pumps or possessing each one of the operons from Pseudomonas aeruginosa PAO1. The drug specificity of MexAB-OprM, MexXY-OprM and MexCD-OprJ was investigated. Surprisingly, we found that the MexCD-OprJ was an inducible pump, inducers of which were tetraphenylphosphonium chloride, ethidium bromide, rhodamine 6G and acriflavine. Fluoroquinolones, chloramphenicol, erythromycin and tetracycline were not inducers although they were substrates of MexCD-OprJ.

Retrospective analysis of 1502 patients with facial fractures.

A total of 1502 patients with facial fractures treated between 1981 and 1996 were retrospectively analysed. The male: female ratio was 2.8:1 and the largest subgroup of patients was between 10 and 29 years of age. The most common cause of injury was traffic accidents (52%) involving motorcycles, bicycles or automobiles. Other common causes included, in descending order, falls (16.6%), assaults (15.5%) and sports (9.7%). Isolated mandibular fractures were most common (56.9%), followed by isolated midface fractures (25.9%). The percentage of fractures involving both the midface and mandible was 6.7, and that of isolated alveolar fractures was 10.5.

Transient interhemispheric neuronal synchrony correlates with object recognition.

Object recognition might be achieved by the recreation of a meaningful internal image from visual fragments. This recreation might be achieved by neuronal synchronization that has been proposed as a solution for the perceptual binding problem. In this study, we evaluated synchronization between the occipitotemporal regions bilaterally using electroencephalograms during several visual recognition tasks. Conscious recognition of familiar objects spanning the visual midline induced transient interhemispheric electroencephalographic coherence in the alpha band, which did not occur with meaningless objects or with passive viewing. Moreover, there was no interhemispheric coherence when midline objects were not recognized as meaningful or when familiar objects were presented in one visual hemifield. These data suggest a close link between site-specific interregional synchronization and object recognition.

Information flow from the sensorimotor cortex to muscle in humans.

OBJECTIVES: To investigate the physiologic mechanism of human electroencephalogram-electromyogram (EEG-EMG) coherence, the directed transfer function (DTF) based on a multivariate autoregressive (MVAR) model was computed. METHODS: Fifty-six channel EEG and EMG of the right abductor pollicis brevis muscle during a weak tonic contraction were recorded in 6 normal volunteers. The EEG over the left sensorimotor area and the rectified EMG were used to compute coherence and DTF. RESULTS: EEG-EMG coherence was observed at the peak frequency of 15-29 Hz (mean 18.5 Hz). The peak frequency of DTF from EEG to EMG was 12-27 Hz (mean 17.8 Hz). DTF from EEG to EMG was significantly larger than that from EMG to EEG at 19-30 and 45-50 Hz (P<0.05). CONCLUSIONS: The present findings suggest that the EEG-EMG coupling mechanism for the 19 Hz or higher frequency might differ from that for the lower frequency. Directional information flow from EEG to EMG in the former frequency range likely reflects the motor control command. The finding of the directional information flow from EEG to EMG within the gamma band indicates that 40 Hz EEG-EMG coherence is not specific to the muscle Piper rhythm which is seen only with strong contraction.

Aberrant expression of neurotrophic factors in the ventricular progenitor cells of infant congenitally hydrocephalic rats.

OBJECTS: This study was conducted to investigate the roles of neurotrophic factors in the development of hydrocephalus in HTX rats. METHODS: Expressions of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and fibroblast growth factor (FGF)-1 were examined immunohistochemically in the cerebral cortex and ventricular zone of 6-day-old rats with congenital hydrocephalus (HTX rats). In the ventricular zone of hydrocephalic rats, potent BDNF-like immunoreactivity (-LI) and weak but significant signals for NT-3- and FGF-1-LIs were observed. However, no significant signals were detected in non-HTX rats. A small subpopulation of ventricular cells was positive for microtubule-associated protein 2 in HTX and non-HTX rats. The positive cells in the HTX rats had neurites much longer than those in the non-HTX animals, suggesting that some ventricular cells of the hydrocephalics had ectopically differentiated into mature neurons. CONCLUSIONS: This abnormal differentiation may have been responsible for the aberrant expressions of neurotrophic factors. In contrast, the cerebral neuronal layers did not show such prominent alterations in neurotrophic factor expression.

Enhanced expression and DNA binding activity of two CCAAT/enhancer-binding protein isoforms, C/EBPbeta and C/EBPdelta, in rheumatoid synovium.

OBJECTIVE: To investigate the activation and expression of CCAAT/enhancer-binding proteins (C/EBP), especially C/EBPbeta and -delta, in rheumatoid synovium, and their pathogenic implications in rheumatoid arthritis (RA). METHODS: The activation of C/EBPbeta and -delta was assessed in synovial tissues from patients with RA by electrophoretic mobility shift assay (EMSA); DNA binding activity of C/EBPs was evaluated by measuring EMSA band density. The expression and distribution of C/EBPbeta and -delta in synovial tissues were examined by immunohistochemistry analysis. As a control, synovial tissues from patients with osteoarthritis (OA) were studied. RESULTS: Enhanced DNA binding activity of C/EBPbeta and -delta, 2 major members of the C/EBP family, was detected in synovial tissues from RA patients, while synovial tissues from the patients with OA showed only faint or marginal activity (mean +/- SEM arbitrary units [AU] RA 23.3 +/- 11.7 in RA versus 4.5 +/- 1.3 in OA; P < 0.05). Moreover, the binding activities of the C/EBP proteins were correlated with both serum C-reactive protein levels (r = 0.62, P < 0.05) and synovial interleukin-6 messenger RNA levels (r = 0.60, P < 0.05). In immunohistochemistry studies, C/EBPbeta and -delta were detected predominantly in the rheumatoid synovial lining cells (both CD14+ and CD14- cells). CONCLUSION: C/EBPbeta and -delta may contribute to the pathology of rheumatoid synovitis.

Functional coupling of human right and left cortical motor areas demonstrated with partial coherence analysis.

Although a linear correlation between oscillatory activities in the right and left motor cortices during movements has been shown in monkeys, there has been a debate whether scalp-recorded EEG coherence in human reflects a similar association. By applying partial coherence analysis, we demonstrated that interhemispheric coherence during movements cannot be explained by contamination from the occipital alpha rhythm or common reference signal. A significant increase of net interhemispheric communication in the beta1 band was shown during movements. We propose that the partial coherence method can be a useful tool to measure cortico-cortical functional coupling reliably.