A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.

Differences in Tissue Oxygenation, Perfusion and Optical Properties in Brain Areas Affected by Stroke: A Time-Resolved NIRS Study.

Near infrared spectroscopy (NIRS) has been applied to measurements of cerebral blood oxygenation (CBO) in normal subjects and patients with various brain disorders including cerebrovascular diseases. However, it is not known whether NIRS allow us to measure CBO correctly in patients with abnormal cortices where optical characteristics such as optical pathlength (OP) may differ from those in normal cortex. In the present study, employing a time-resolved NIRS (TNIRS), we compared baseline hemoglobin (Hb) concentrations and OPs between normal and abnormal cortices in chronic stroke patients. We studied five patients with chronic cerebral infarction (two males, three females, age 59.0 ± 24.2 years) who were admitted to the University Hospital of Fukushima Prefectural Medical University. Employing TNIRS (TRS-20, Hamamatsu Photonics), we measured baseline Hb concentrations and OPs (760, 800, 830 nm) at various positions on the head. We observed that deoxy-Hb concentrations were significantly lower on the affected side (p < 0.01), and the tissue oxygen saturation was significantly higher than that on the affected side (p < 0.01), suggesting that oxygen consumption was reduced on the affected side. In addition, the OPs (760, 800 nm) were significantly longer on the affected side (p < 0.05); these changes might be caused by a possible increase of cerebrospinal fluid layer associated with brain tissue degeneration by ischemia. The present results suggest that NIRS should be performed on patients with abnormal cerebral cortices, giving special consideration to the possible difference in optical characteristics between normal and abnormal brain tissues.

Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease.

AIMS: Glutamate neurotoxicity plays an important role in the pathogenesis of various neurodegenerative disorders. Many studies have demonstrated that glutamate transporter-1 (GLT-1), the dominant astrocytic glutamate transporter, is significantly reduced in the cerebral cortex of patients with Alzheimer's disease (AD), suggesting that glutamate-mediated excitotoxicity might contribute to the pathogenesis of AD. In a previous study, we have demonstrated marked alterations in the expression of the astrocytic water channel protein aquaporin-4 (AQP4) in relation to amyloid ß deposition in human AD brains. As a functional complex, GLT-1 and AQP4 in astrocytes may play a neuroprotective role in the progression of AD pathology. However, few studies have examined the correlation between the expression of GLT-1 and that of AQP4 in human AD brain. METHODS: Here, using immunohistochemistry with antibodies against GLT-1 and AQP4, we studied the expression levels and distribution patterns of GLT-1 in areas showing various patterns of AQP4 expression in autopsied temporal lobes from eight patients with AD and five controls without neurological disorders. RESULTS: GLT-1 staining in the control group was present throughout the neocortex as uniform neuropil staining with co-localized AQP4. The AD group showed a significant reduction in GLT-1 expression, whereas cortical AQP4 immunoreactivity was more intense in the AD group than in the control group. There were two different patterns of GLT-1 and AQP4 expression in the AD group: (i) uneven GLT-1 expression in the neuropil where diffuse but intense AQP4 expression was evident, and (ii) senile plaque-like co-expression of GLT-1 and AQP4. CONCLUSIONS: These findings suggest disruption of glutamate/water homoeostasis in the AD brain.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Non-invasive cerebellar stimulation--a consensus paper.

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

Short-interval intracortical inhibition in Parkinson's disease using anterior-posterior directed currents.

Reduced short-interval intracortical inhibition (SICI) is reported in Parkinson's disease (PD) and is considered to reflect abnormal GABAergic inhibitory system of the primary motor cortex in PD. We have recently shown, however, that SICI using anterior-posterior directed currents in the brain was normal in focal dystonia even though that using posterior-anterior currents was abnormal, indicating that the GABAergic system of the primary motor cortex is largely normal in dystonia. Here, we studied SICI in PD to clarify whether the GABAergic system is completely impaired in PD. We used paired-pulse transcranial magnetic stimulation to study SICI at interstimulus intervals of 3 and 4 ms with anterior-posterior or posterior-anterior directed currents in eight PD patients and ten healthy volunteers. The amount of SICI with posterior-anterior directed currents was reduced in PD patients compared with healthy volunteers; in contrast, SICI studied with anterior-posterior directed currents was normal in PD patients. These observations may be due to the difference in I-wave composition generated by the two directed currents and/or the difference in responsible inhibitory interneurons for the inhibition between the two current directions. We suggest that some or a part of inhibitory interneurons are not involved in PD. This discrepancy between SICI using posterior-anterior and anterior-posterior directed currents experiments may provide additional information about the circuits of the motor cortex.

Triad stimulation frequency for cortical facilitation in cortical myoclonus.

BACKGROUND: Abnormally enhanced cortical rhythmic activities have been reported in patients with cortical myoclonus. We recently reported a new triad-conditioning transcranial magnetic stimulation (TMS) method to detect the intrinsic rhythms of the primary motor cortex (M1). Triad-conditioning TMS revealed a 40-Hz intrinsic rhythm of M1 in normal subjects. In this investigation, we study the motor cortical facilitation induced by rhythmic triple TMS pulses (triad-conditioning TMS) in patients with cortical myoclonus. METHODS: Subjects were 7 patients with cortical myoclonus (28-74 years old) and 13 healthy volunteers (30-71 years old). Three conditioning stimuli over M1 at the intensity of 110% active motor threshold preceded the test TMS at various interstimulus intervals corresponding to 10-200 Hz. The resulting amplitudes of conditioned motor evoked potentials recorded from the contralateral hand muscle were compared with those evoked by the test stimulus alone. RESULTS: The facilitation at 25 ms (40 Hz) observed in normal subjects was absent in patients with cortical myoclonus. Instead, triad-conditioning TMS induced facilitation at a 40 ms interval (25 Hz) in cortical myoclonus. DISCUSSIONS: This change in the timing of facilitation may be explained by a shift of the most preferential intrinsic rhythm of M1, or by some dysfunction in the interneuronal network in cortical myoclonus.

Effects of STN stimulation on the initiation and inhibition of saccade in Parkinson disease.

OBJECTIVES: The basal ganglia (BG) play an important role in controlling saccades. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used as a treatment of Parkinson disease (PD) by altering the function of the BG. Nevertheless, the effects of STN DBS on saccade performance are not fully clarified in a systematic manner. In this study, we examined the effects of bilateral STN DBS on both the initiation and inhibition of saccades in PD. METHODS: Thirty-two patients with PD performed 4 oculomotor tasks. Two tasks (visually guided saccades and gap saccades) were reflexive and 2 (memory-guided saccades [MGS] and antisaccades) were volitional. While taking their regular doses of antiparkinsonian drugs, patients performed these tasks under 2 conditions: during DBS (DBS-on condition) and without DBS (DBS-off condition). Fifty-one age-matched subjects served as controls. RESULTS: In the DBS-on condition, parameters of saccade initiation were improved in all tasks, with shorter latencies and increased amplitudes, except for MGS latency. STN DBS improved the ability to suppress unwanted saccades to the cue stimulus in the MGS task. However, it did not suppress prosaccades during the antisaccade task. CONCLUSIONS: These results suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects the neural pathway common to both reflexive and volitional saccades, possibly by acting on the STN-substantia nigra pars reticulata-superior colliculi pathway. STN DBS may set the functional level of the superior colliculi appropriate for both saccade initiation and inhibition through this pathway. These findings provide novel insights into the pathophysiology of Parkinson disease and may yield better treatment strategies.

Difference in intracortical inhibition of the motor cortex between cortical myoclonus and focal hand dystonia.

OBJECTIVE: The short interval intracortical inhibition (SICI) of the motor cortex (M1) is reduced in both cortical myoclonus and focal hand dystonia. This reduction has been attributed to the dysfunction of GABAergic system within the motor cortex. However, the precise mechanisms underlying the reduction may not be entirely identical in these two disorders, being due to primary pathological involvement in M1 or secondary to functional changes outside M1. The aim of this study was to elucidate possible differences in intracortical inhibition between these two disorders. METHODS: Subjects were 11 patients with benign myoclonus epilepsy, 7 with focal hand dystonia, and 11 normal volunteers. We studied SICI using anterior-posterior (AP) directed and posterior-anterior (PA) directed induced currents in the brain. RESULTS: In both disorders, SICI with PA-directed currents was reduced as reported previously. In contrast, SICI studied with AP currents was normal in patients with focal hand dystonia, but reduced in patients with cortical myoclonus. CONCLUSIONS: The difference between the two disorders might reflect the underlying pathological difference. In cortical myoclonus, the inhibitory interneurons of the motor cortex are affected, whereas the same interneurons are intact in dystonia. The difference in SICI induced by AP and PA directed currents in dystonia may be explained by the following possibilities: the difference in composition of I-waves contributing to EMG generation and the difference in modulation of the interneuronal activity by voluntary contraction. These changes may be secondary to dysregulation of the motor cortex by the basal ganglia or related cortices in dystonia. SIGNIFICANCE: The SICI using AP directed currents together with the conventional SICI using PA directed currents was able to demonstrate some difference in the intrinsic circuits of M1 between myoclonus and focal hand dystonia. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.

A case of bilateral parietal cortical laminar necrosis with a loss of vertiginous sensation.

BACKGROUND: Animal experiments demonstrated that there are vestibular cortical areas at the parietal cortex. Moreover, in humans, recent functional neuroimaging studies revealed that caloric stimulation activated the parietoinsular vestibular cortex and optokinetic stimulation activated the parieto-occipital cortex. These activations indicate that the parietal vestibular areas play some role in nystagmus generation or in spatial information processing in the eye movement tasks. AIMS OF THE STUDY: The aim of this communication was to present a patient giving some information about parietal cortical function in nystagmus production and vertigo. CASE: We report a 51-year-old, heavy alcoholic man with Bálint syndrome, constructional disability, limb-kinetic apraxia and ideo-motor apraxia. Brain magnetic resonance imaging demonstrated bilateral parietal cortical laminar necrosis anterior to the parieto-occipital sulci without any involvement of the primary sensory and parietoinsular cortices. Optokinetic nystagmus (OKN) was not elicited whereas cold caloric stimulation fully evoked nystagmus toward the opposite side with oscillopsia when eyes opened. However, he did not feel vertiginous sensation when the eyes were closed. CONCLUSIONS: These findings suggest that the parietal cortices are indispensable for OKN production and vertiginous sensation.

Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation.

OBJECTIVE: To assess corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS) by correlating diffusion tensor imaging (DTI) measures with intra- and extracranial central motor conduction time (CMCT) and clinical features of the patients. METHODS: We investigated 31 patients with ALS and 31 normal volunteers by DTI and measured fractional anisotropy (FA) within the corticospinal tracts and in the extramotor white matter. We measured CMCT for the first dorsal interosseous muscle and segmented it into cortical-brainstem (CTX-BS CT) and brainstem-cervical root (BS-CV CT) conduction times by magnetic brainstem stimulation at the foramen magnum level. Clinical status of each patient was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and upper motor neuron (UMN) score devised for this study. RESULTS: We found a significant decrease of mean FA in all regions of the corticospinal tracts in patients with ALS as compared with controls. We found that FA along the corticospinal tract decreased significantly with higher UMN scores. There was no significant correlation between FA and ALSFRS-R, to which both upper and lower motoneuron involvements contribute. FA showed a significant correlation with the intracranial part of the central motor conduction (CTX-BS CT) but not with the extracranial conduction time. CONCLUSIONS: Fractional anisotropy reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of upper motor neuron impairment in amyotrophic lateral sclerosis.

Paired stimulation study of the median nerve sensory action potential in diabetic patients.

OBJECTIVES: Conventional nerve conduction studies (NCS) are not sensitive to detect mild diabetic neuropathy. In order to detect subtle changes, we compared the conventional NCS with the relative refractory period (RRP) measurement of the median sensory nerve action potential by a paired stimulation method. METHODS: Subjects were 29 diabetic patients whose conventional NCS were all normal. They were divided into two groups: neurologically symptomatic and asymptomatic groups. Twenty-eight age-matched control subjects were also studied. RESULTS: The RRP of the symptomatic diabetic patients (5.9 +/- 0.5 ms) and that of the asymptomatic patients (5.6 +/- 0.5 ms) was significantly longer than that of the control subjects (4.9 +/- 0.6 ms). There was no significant difference in RRP between the symptomatic and asymptomatic patients. This may be due to the fact that NCS reflects mainly large myelinated fiber function and early symptoms represent mainly thin myelinated or unmyelinated fiber function. CONCLUSIONS: The RRP measurement could reveal some mild involvement of peripheral nerves undetectable by conventional NCS, even though they caused no clinical symptoms.

Intracortical inhibition of the motor cortex in Segawa disease (DYT5).

BACKGROUND: Segawa disease (autosomal dominant guanosine triphosphate cyclohydrolase I [GTP-I] deficiency, DYT5) is a hereditary dopa-responsive generalized dystonia. OBJECTIVE: To investigate the pathophysiologic mechanisms for dystonia in Segawa disease, we studied intracortical inhibition of the primary motor cortex in patients with Segawa disease. METHODS: We studied 9 patients with Segawa disease (8 genetically confirmed patients and 1 with abnormally low GTP-I activity) and 12 age-matched normal control subjects. We studied the active motor threshold (AMT) using single pulse transcranial magnetic stimulation (TMS) and the short-interval intracortical inhibition (SICI) of the motor cortex using the previously reported paired pulse TMS method. Responses were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. RESULTS: The AMT was not significantly different between the patients and normal subjects. For both studied muscles, in Segawa disease, normal amount of SICI was evoked at interstimulus intervals (ISIs) of 1 to 4 msec even though they had dystonia in those muscles. CONCLUSION: Normal SICI of the motor cortex in Segawa disease stands in remarkable contrast to the previously reported reduction of SICI in focal dystonia. This suggests that the gamma-aminobutyric acid A system of the motor cortex is intact in Segawa disease. The pathophysiologic mechanisms for dystonia must be partly different between Segawa disease and focal dystonia.

Cognitive impairment and diffuse white matter atrophy in alcoholics.

OBJECTIVE: Diffuse brain white matter atrophy is often seen in chronic alcoholics, but its relation with cognitive impairment remains to be solved. In order to address this issue, in alcoholics with cognitive impairment at different levels, we studied relations of the central sensory conduction time (CSCT) or brain magnetic resonance imaging (MRI) findings with the cognitive function. METHODS: Subjects were 35 alcoholics with mild cognitive impairment (mini-mental state examination score, MMSE, >/=24; mean+/-SD, 27.7+/-1.9), 12 with moderate to severe cognitive impairment (MMSE<24; 20.3+/-2.7), 15 with Alzheimer's disease (AD) (MMSE, 18.9+/-4.3) (disease control) and 20 healthy volunteers (MMSE, 28.5+/-1.6) (normal control). Median nerve SEPs were recorded in the all subjects, and the latencies and amplitudes of their N9, N11, P13/14, N20 and P25 components were measured. The ventriculocranial ratio (VCR) and the width of cortical sulci were measured on MRIs. These physiological parameters and MRI findings were compared between the 4 groups of the subject, and correlations between those all features were also analyzed. RESULTS: CSCT and VCR were significantly greater in alcoholics with moderate to severe cognitive impairment than those in the other 3 groups. Pearson's product-moment correlation analyses of the alcoholics disclosed that both the CSCT and VCR had significant negative correlations with the MMSE score. Moreover, the CSCT and VCR were positively correlated. CONCLUSIONS: Both physiological and morphological estimates of the white matter function (CSCT and VCR) had a significant correlation with the cognitive dysfunction. SIGNIFICANCE: The diffuse white matter atrophy may be one of the factors causing cognitive impairment in chronic alcoholics.

Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. OBJECTIVE: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). METHODS: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. RESULTS: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. CONCLUSIONS: Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.

Stiff-person syndrome associated with invasive thymoma: a case report.

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.