Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial.

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, - 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

Utilization of three-dimensional fusion images with high-resolution computed tomography angiography for preoperative evaluation of microvascular decompression: patient series.

BACKGROUND: High-resolution computed tomography (CT), outfitted with a 0.25-mm detector, has superior capability for identifying microscopic anatomical structures compared to conventional CT. This study describes the use of high-resolution computed tomography angiography (CTA) for preoperative microvascular decompression (MVD) assessment and explores the potential effectiveness of three-dimensional (3D) image fusion with magnetic resonance imaging (MRI) by comparing it with traditional imaging methods. OBSERVATIONS: Four patients who had undergone preoperative high-resolution CTA and MRI for MVD at Osaka University Hospital between December 2020 and March 2022 were included in this study. The 3D-reconstructed images and intraoperative findings were compared. One patient underwent conventional CTA, thus allowing for a comparison between high-resolution and conventional CTA in terms of radiation exposure and vascular delineation. Preoperative simulations reflected the intraoperative findings for all cases; small vessel compression of the nerve was identified preoperatively in two cases. LESSONS: Compared with conventional CTA, high-resolution CTA showed superior vascular delineation with no significant change in radiation exposure. The use of high-resolution CTA with reconstructed 3D fusion images can help to simulate prior MVD. Knowing the location of the nerves and blood vessels can perioperatively guide neurosurgeons.

White matter microstructural alterations in patients with neuropathic pain after spinal cord injury: a diffusion tensor imaging study.

Background: Through contrastive analysis, we aimed to identify the white matter brain regions that show microstructural changes in patients with neuropathic pain (NP) after spinal cord injury (SCI). Methods: We categorized patients with SCI into NP (n = 30) and non-NP (n = 15) groups. We extracted diffusion tensor maps of fractional anisotropy (FA) and mean (MD), axial (AD), and radial (RD) diffusivity. A randomization-based method in tract-based spatial statistics was used to perform voxel-wise group comparisons among the FA, MD, AD, and RD for nonparametric permutation tests. Results: Atlas-based analysis located significantly different regions (p < 0.05) in the appointed brain atlas. Compared to the non-NP group, the NP group showed higher FA in the posterior body and splenium of the corpus callosum and higher AD in the corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, sagittal stratum, external capsule, cingulum, fornix/stria terminalis, superior longitudinal fasciculus, and uncinate fasciculus. Conclusion: The results demonstrated that compared with the non-NP group, NP pathogenesis after SCI was potentially related to higher values in FA that are associated with microstructural changes in the posterior body and splenium of the corpus callosum, which could be regarded as central sensitization or network hyperexcitability.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Excessive excitability of inhibitory cortical circuit and disturbance of ballistic targeting movement in degenerative cerebellar ataxia.

This study aimed to investigate abnormalities in inhibitory cortical excitability and motor control during ballistic-targeting movements in individuals with degenerative cerebellar ataxia (DCA). Sixteen participants took part in the study (DCA group [n = 8] and healthy group [n = 8]). The resting motor-threshold and cortical silent period (cSP) were measured in the right-hand muscle using transcranial magnetic stimulation over the left primary motor cortex. Moreover, the performance of the ballistic-targeting task with right wrist movements was measured. The Scale for the Assessment and Rating of Ataxia was used to evaluate the severity of ataxia. The results indicated that the cSP was significantly longer in participants with DCA compared to that in healthy controls. However, there was no correlation between cSP and severity of ataxia. Furthermore, cSP was linked to the ballistic-targeting task performance in healthy participants but not in participants with DCA. These findings suggest that there is excessive activity in the gamma-aminobutyric acid-mediated cortical inhibitory circuit in individuals with DCA. However, this increase in inhibitory activity not only fails to contribute to the control of ballistic-targeting movement but also shows no correlation with the severity of ataxia. These imply that increased excitability in inhibitory cortical circuits in the DCA may not contribute the motor control as much as it does in healthy older adults under limitations associated with a small sample size. The study's results contribute to our understanding of motor control abnormalities in people with DCA and provide potential evidence for further research in this area.

Characteristics of Pain During MRI-Guided Focused Ultrasound Thalamotomy.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) has become popular as an incisionless mode of neurosurgical treatment. However, head pain during sonication is common and its pathophysiology remains poorly understood. OBJECTIVE: To explore the characteristics of head pain occurring during MRgFUS thalamotomy. METHODS: Our study comprised 59 patients who answered questions about the pain they experienced during unilateral MRgFUS thalamotomy. The location and features of pain were investigated using a questionnaire including the numerical rating scale (NRS) to estimate maximum pain intensity and the Japanese version of the Short Form of McGill Pain Questionnaire 2 to evaluate the quantitative and qualitative dimensions of pain. Several clinical factors were investigated for possible correlation with pain intensity. RESULTS: Forty-eight patients (81%) reported sonication-related head pain, and the degree of pain was severe (NRS score ≥ 7) in 39 patients (66%). The distribution of sonication-related pain was "localized" in 29 (49%) and "diffuse" in 16 (27%); the most frequent location was the "occipital" region. The pain features most frequently reported were those in the "affective" subscale of the Short Form of McGill Pain Questionnaire 2. Patients with diffuse pain had a higher NRS score and lower skull density ratio than did patients with localized pain. The NRS score negatively correlated with tremor improvement at 6 months post-treatment. CONCLUSION: Most patients in our cohort experienced pain during MRgFUS. The distribution and intensity of pain varied according to the skull density ratio, indicating that the pain might have had different origins. Our results may contribute to the improvement of pain management during MRgFUS.

Cerebrospinal fluid amyloid beta and response of cognition to a tap test in idiopathic normal pressure hydrocephalus: a case-control study.

OBJECTIVES: To examine the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and tap test response to elucidate the effects of comorbidity of AD in idiopathic normal-pressure hydrocephalus (iNPH). DESIGN: Case-control study. SETTING: Osaka University Hospital. PARTICIPANTS: Patients with possible iNPH underwent a CSF tap test. MEASUREMENTS: Concentrations of amyloid beta (Aß) 1-40, 1-42, and total tau in CSF were measured. The response of tap test was judged using Timed Up and Go test (TUG), 10-m reciprocation walking test (10MWT), Mini-Mental State Examination (MMSE), and iNPH grading scale. The ratio of Aß1-42 to Aß1-40 (Aß42/40 ratio) and total tau concentration was compared between tap test-negative (iNPH-nTT) and -positive (iNPH-pTT) patients. RESULTS: We identified 27 patients as iNPH-nTT and 81 as iNPH-pTT. Aß42/40 ratio was significantly lower (mean [SD] = 0.063 [0.026] vs. 0.083 [0.036], p = 0.008), and total tau in CSF was significantly higher (mean [SD] = 385.6 [237.2] vs. 293.6 [165.0], p = 0.028) in iNPH-nTT than in iNPH-pTT. Stepwise logistic regression analysis revealed that low Aß42/40 ratio was significantly associated with the negativity of the tap test. The response of cognition was significantly related to Aß42/40 ratio. The association between Aß42/40 ratio and tap test response, especially in cognition, remained after adjusting for disease duration and severity at baseline. CONCLUSIONS: A low CSF Aß42/40 ratio is associated with a poorer cognitive response, but not gait and urinary response, to a tap test in iNPH. Even if CSF biomarkers suggest AD comorbidity, treatment with iNPH may be effective for gait and urinary dysfunction.

Impact of Repetitive Transcranial Magnetic Stimulation to the Cerebellum on Performance of a Ballistic Targeting Movement.

This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on changes in motor performance during a series of repetitive ballistic-targeting tasks. Twenty-two healthy young adults (n = 12 in the active-rTMS group and n = 10 in the sham rTMS group) participated in this study. The participants sat on a chair in front of a monitor and fixed their right forearms to a manipulandum. They manipulated the handle with the flexion/extension of the wrist to move the bar on the monitor. Immediately after a beep sound was played, the participant moved the bar as quickly as possible to the target line. After the first 10 repetitions of the ballistic-targeting task, active or sham rTMS (1 Hz, 900 pulses) was applied to the right cerebellum. Subsequently, five sets of 100 repetitions of this task were conducted. Participants in the sham rTMS group showed improved reaction time, movement time, maximum velocity of movement, and targeting error after repetition. However, improvements were inhibited in the active-rTMS group. Low-frequency cerebellar rTMS may disrupt motor learning during repetitive ballistic-targeting tasks. This supports the hypothesis that the cerebellum contributes to motor learning and motor-error correction in ballistic-targeting movements.

Tight adhesions after spinal cord stimulation observed during dorsal root entry zone lesioning for pain after spinal root avulsion: illustrative cases.

BACKGROUND: Patients often experience strong shooting pains after spinal root avulsion. The efficacy of spinal cord stimulation (SCS) for this type of pain is inconsistent; however, dorsal root entry zone (DREZ) lesioning (DREZ-lesion) has often proven to be an effective treatment modality. The authors report two cases in which DREZ-lesion was performed to treat pain after spinal root avulsion after implantation of SCS, but the operations were challenging due to strong adhesions. OBSERVATIONS: The authors present two cases of patients with pain after spinal root avulsion in whom SCS implantation was only temporarily effective. Patients complained of persistent and paroxysmal shooting pains in the upper extremities. SCS removal and DREZ-lesion were performed, but adhesions in the epidural and subdural space contacting the leads were strong, making it difficult to expose the DREZ. LESSONS: Although adhesions around the spinal cord can be caused by trauma, the authors believe that in these cases, the adhesions could have been caused by the SCS leads. There are few previous reports confirming the efficacy of SCS in treating pain after spinal root avulsion; therefore, caution is required when considering SCS implantation.

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan.

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS.

Neurofeedback Training without Explicit Phantom Hand Movements and Hand-Like Visual Feedback to Modulate Pain: A Randomized Crossover Feasibility Trial.

Phantom limb pain is attributed to abnormal sensorimotor cortical representations, although the causal relationship between phantom limb pain and sensorimotor cortical representations suffers from the potentially confounding effects of phantom hand movements. We developed neurofeedback training to change sensorimotor cortical representations without explicit phantom hand movements or hand-like visual feedback. We tested the feasibility of neurofeedback training in fourteen patients with phantom limb pain. Neurofeedback training was performed in a single-blind, randomized, crossover trial using two decoders constructed using motor cortical currents measured during phantom hand movements; the motor cortical currents contralateral or ipsilateral to the phantom hand (contralateral and ipsilateral training) were estimated from magnetoencephalograms. Patients were instructed to control the size of a disk, which was proportional to the decoding results, but to not move their phantom hands or other body parts. The pain assessed by the visual analogue scale was significantly greater after contralateral training than after ipsilateral training. Classification accuracy of phantom hand movements significantly increased only after contralateral training. These results suggested that the proposed neurofeedback training changed phantom hand representation and modulated pain without explicit phantom hand movements or hand-like visual feedback, thus showing the relation between the phantom hand representations and pain. PERSPECTIVE: Our work demonstrates the feasibility of using neurofeedback training to change phantom hand representation and modulate pain perception without explicit phantom hand movements and hand-like visual feedback. The results enhance the mechanistic understanding of certain treatments, such as mirror therapy, that change the sensorimotor cortical representation.

Excess intracellular ATP causes neuropathic pain following spinal cord injury.

Intractable neuropathic pain following spinal cord injury (NP-SCI) reduces a patient's quality of life. Excessive release of ATP into the extracellular space evokes neuroinflammation via purinergic receptor. Neuroinflammation plays an important role in the initiation and maintenance of NP. However, little is known about whether or not extracellular ATP cause NP-SCI. We found in the present study that excess of intracellular ATP at the lesion site evokes at-level NP-SCI. No significant differences in the body weight, locomotor function, or motor behaviors were found in groups that were negative and positive for at-level allodynia. The intracellular ATP level at the lesion site was significantly higher in the allodynia-positive mice than in the allodynia-negative mice. A metabolome analysis revealed that there were no significant differences in the ATP production or degradation between allodynia-negative and allodynia-positive mice. Dorsal horn neurons in allodynia mice were found to be inactivated in the resting state, suggesting that decreased ATP consumption due to neural inactivity leads to a build-up of intracellular ATP. In contrast to the findings in the resting state, mechanical stimulation increased the neural activity of dorsal horn and extracellular ATP release at lesion site. The forced production of intracellular ATP at the lesion site in non-allodynia mice induced allodynia. The inhibition of P2X4 receptors in allodynia mice reduced allodynia. These results suggest that an excess buildup of intracellular ATP in the resting state causes at-level NP-SCI as a result of the extracellular release of ATP with mechanical stimulation.

Cerebellar repetitive transcranial magnetic stimulation modulates the motor learning of visually guided voluntary postural control task.

We investigated whether vermal cerebellar low-frequency repetitive transcranial magnetic stimulation (crTMS) affects motor learning of visually guided postural tracking training (VTT) using foot center of pressure (COP) as well as the stability and sensory contribution of upright standing. Twenty-one healthy volunteers participated (10 in the sham-crTMS group and 11 in the active-crTMS group). For VTT, participants stood on the force plate 1.5 m from the monitor on which the COP and target moved in a circle. Participants tracked the target with their own COP for 1 min, and 10 VTT sessions were conducted. The tracking error (TE) was compared between trials. Active- or sham-crTMS sessions were conducted prior to VTT. At baseline (before crTMS), pre-VTT (after crTMS), and post-VTT, the COP trajectory during upright static standing under four conditions (eyes, open/closed; surface, hard/rubber) was recorded. Comparison of the length of the COP trajectory or path and sensory-contribution-rate showed no significant difference between baseline and pre- and post-VTT. There was a significant decrease in TE in the sham-crTMS but not in the active-crTMS group. VTT and crTMS did not immediately affect the stability and sensory contribution of upright standing; however, crTMS immediately affected motor learning. The vermal cerebellum may contribute to motor learning of voluntary postural control.

Altered Thalamic Connectivity Due to Focused Ultrasound Thalamotomy in Patients with Essential Tremor.

BACKGROUND: Although stereotactic ablation surgery is known to ameliorate involuntary movement dramatically, little is known regarding alterations in whole-brain networks due to disruption of the deep brain nucleus. To explore changes in the whole-brain network after thalamotomy, we analyzed structural and functional connectivity alterations using resting-state functional magnetic resonance imaging and diffusion tensor imaging in patients with essential tremor who had undergone focused ultrasound (FUS) thalamotomy. METHODS: Seven patients with intractable essential tremors and 7 age-matched healthy controls were enrolled in the study. The tremor score in essential tremor patients was assessed, and resting-state functional magnetic resonance imaging and diffusion tensor imaging were performed before and 3 months after left ventral intermediate nucleus thalamotomy using FUS. RESULTS: There was a significant improvement in the tremor of the right hand after FUS thalamotomy. Seed-based functional connectivity analysis revealed a significant increase in functional connectivity between the left thalamus and the caudal part of the dorsal premotor cortex after FUS thalamotomy. Structural connectivity analysis did not detect statistically significant changes between before and after FUS. There was no correlation between the changes in functional connectivity and tremor score. CONCLUSIONS: Although the number of cases is small, our results show that functional connectivity between the thalamus and the premotor cortex increases after the amelioration of tremors by FUS thalamotomy. The lack of correlation between increased functional connectivity and clinical tremor scores suggests that the observed increase in functional connectivity may be a compensatory change in the secondary sensorimotor changes that occur after thalamotomy.

Analgesic Effects of Repetitive Transcranial Magnetic Stimulation at Different Stimulus Parameters for Neuropathic Pain: A Randomized Study.

OBJECTIVES: The aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain. MATERIALS AND METHODS: We conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz with 500 pulses per session, 10-Hz with 500 pulses per session, 10-Hz with 2000 pulses per session, and sham stimulation. Analgesic effects were assessed by determining the visual analog scale (VAS) pain intensity score and Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score immediately before and immediately after intervention. RESULTS: We enrolled 22 adults (age: 59.8 ± 12.1 years) with intractable neuropathic pain. Linear-effects models showed significant effects of the stimulation condition on changes in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.01). Tukey multiple comparison tests revealed that 10-Hz rTMS with 2000 pulses provided better pain relief than sham stimulation, with greater decreases in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.02). CONCLUSIONS: The results of this study suggest that high-dose stimulation (specifically, 10-Hz rTMS at 2000 pulses) is more effective than lower-dose stimulation for treating neuropathic pain.

Benefit of spinal cord stimulation for patients with central poststroke pain: a retrospective multicenter study.

OBJECTIVE: Spinal cord stimulation (SCS) has been considered an ineffective procedure for patients with central poststroke pain (CPSP). However, recent case series that included small numbers of patients reported the possible efficacy of SCS as a treatment of CPSP. This multicenter retrospective study aimed to examine the outcomes of using SCS to treat patients with CPSP and to explore factors related to outcomes. METHODS: The authors reviewed the medical records of patients with CPSP who underwent SCS to collect data regarding their background, surgical information, and outcomes of SCS at trial stimulation and last follow-up after long-term implantation in six study centers. Outcomes were evaluated with a pain score for intensity (range 0-10) and the Patient Global Impression of Changes (PGIC) scale. Factors associated with outcomes were explored with univariable and multivariable analyses. RESULTS: The authors collected data from a total of 166 patients (mean age 63.4 years; mean pain score at baseline 8.2). Of these patients, 163 underwent trial stimulation. The mean pain score decreased by 42.0%, 104 (64%) patients had ≥ 30% decrease in pain score, and 96 (59%) reported much or very much improved condition on the PGIC scale at trial stimulation. Moreover, 106 (64%) patients underwent long-term implantation of SCS devices. The mean decrease in pain score was 41.4%, 63 (59%) patients continued to show ≥ 30% decrease in pain score at last follow-up, and 60 (56%) reported much or very much improved condition on the PGIC scale at last follow-up (median [range] follow-up period 24 [24-63] months). Eleven device-related complications and 10 permanent explantations were observed. Univariable and multivariable analyses suggested that young age, less sensory disturbance, implantation of cervical leads, treatment of upper-limb pain, and extensive treated regions were associated with satisfactory outcomes at last follow-up after long-term implantation. CONCLUSIONS: These findings indicate that SCS may modestly benefit patients with CPSP. SCS has therapeutic potential for patients with intractable CPSP owing to the lower invasiveness of the SCS procedure and refractory nature of CPSP. Nevertheless, trial stimulation is necessary because of the high initial failure rate.

Difference in Analgesic Effects of Repetitive Transcranial Magnetic Stimulation According to the Site of Pain.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex for neuropathic pain has been shown to be effective, according to systematic reviews and therapeutic guidelines. However, our large, rigorous, investigator-initiated, registration-directed clinical trial failed to show a positive primary outcome, and its subgroup analysis suggested that the analgesic effect varied according to the site of pain. The aim of this study was to investigate the differences in analgesic effects of rTMS for neuropathic pain between different pain sites by reviewing our previous clinical trials. We included three clinical trials in this mini meta-analysis: a multicenter randomized controlled trial at seven hospitals (N = 64), an investigator-initiated registration-directed clinical trial at three hospitals (N = 142), and an exploratory clinical trial examining different stimulation parameters (N = 22). The primary efficacy endpoint (change in pain scale) was extracted for each patient group with pain in the face, upper limb, or lower limb, and a meta-analysis of the efficacy of active rTMS against sham stimulation was performed. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated for pain change using a random-effects model. The analgesic effect of rTMS for upper limb pain was favorable (SMD = -0.45, 95% CI: -0.77 to -0.13). In contrast, rTMS did not produce significant pain relief on lower limb pain (SMD = 0.04, 95% CI: -0.33 to 0.41) or face (SMD = -0.24, 95% CI: -1.59 to 1.12). In conclusion, these findings suggest that rTMS provides analgesic effects in patients with neuropathic pain in the upper limb, but not in the lower limb or face, under the conditions of previous clinical trials. Owing to the main limitation of small number of studies included, many aspects should be clarified by further research and high-quality studies in these patients.

Exploratory study of optimal parameters of repetitive transcranial magnetic stimulation for neuropathic pain in the lower extremities.

INTRODUCTION: Pain relief from repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) is particularly poor in patients with leg pain. The optimal parameters for relieving leg pain remain poorly understood. The purpose of this study was to explore the optimal stimulation parameters of M1-rTMS for patients with leg pain. METHODS: Eleven patients with neuropathic pain in the leg randomly underwent 6 conditions of M1-rTMS with different stimulation intensities, sites, and coil directions, including sham stimulation. The 5 active conditions were as follows: 90% or 110% of the resting motor threshold (RMT) on the M1 hand with an anteroposterior coil direction, 90% or 110% RMT on the M1 foot in the anteroposterior direction, and 90% RMT on the M1 foot in the mediolateral direction. Each condition was administered for 3 days. Pain intensity was evaluated using the Visual Analogue Scale and Short-Form McGill Pain Questionnaire 2 at baseline and up to 7 days after each intervention. RESULTS: Visual Analogue Scale scores were significantly reduced after the following active rTMS conditions: 90% RMT on the M1 hand, 90% RMT on the M1 foot with any coil direction, and 110% RMT on the M1 foot. The Short-Form McGill Pain Questionnaire 2 results were similar to those obtained using the Visual Analogue Scale. The analgesic effect of rTMS with stimulus intensity above the RMT was not superior to that below the RMT. CONCLUSION: We suggest that the optimal stimulation parameters of rTMS for patients with neuropathic pain in the leg may target the M1 foot or M1 hand with an intensity below the RMT.

A multi-site, multi-disorder resting-state magnetic resonance image database.

Machine learning classifiers for psychiatric disorders using resting-state functional magnetic resonance imaging (rs-fMRI) have recently attracted attention as a method for directly examining relationships between neural circuits and psychiatric disorders. To develop accurate and generalizable classifiers, we compiled a large-scale, multi-site, multi-disorder neuroimaging database. The database comprises resting-state fMRI and structural images of the brain from 993 patients and 1,421 healthy individuals, as well as demographic information such as age, sex, and clinical rating scales. To harmonize the multi-site data, nine healthy participants ("traveling subjects") visited the sites from which the above datasets were obtained and underwent neuroimaging with 12 scanners. All participants consented to having their data shared and analyzed at multiple medical and research institutions participating in the project, and 706 patients and 1,122 healthy individuals consented to having their data disclosed. Finally, we have published four datasets: 1) the SRPBS Multi-disorder Connectivity Dataset 2), the SRPBS Multi-disorder MRI Dataset (restricted), 3) the SRPBS Multi-disorder MRI Dataset (unrestricted), and 4) the SRPBS Traveling Subject MRI Dataset.

[Stereotactic Surgery for Tremor].

Although tremor is one of the most common movement disorders, there are many different types, and proper diagnosis is important for appropriate treatment. Action tremor has a significant impact on daily life, but the effectiveness of medical treatment is insufficient, and surgery is often the treatment of choice. Surgical treatment is effective in suppressing tremor, and a large percentage of tremors can be adequately controlled. Currently available surgical treatments for tremor include the ventral intermediate nucleus of thalamus-deep brain stimulation(DBS), radiofrequency(RF)-thalamotomy, focused ultrasound(FUS)-thalamotomy, and gamma knife thalamotomy. DBS is often considered the first choice for surgical treatment due to the number of past cases in which DBS has been applied, reported evidence, long-term efficacy, safety, adjustability, and the possibility of bilateral treatment, but RF-thalamotomy is also expected to improve efficacy and safety because of recent advancements in coagulation technology and the accumulation of anatomical knowledge regarding the target nucleus. In addition, the number of cases in which FUS-thalamotomy has been applied has been increasing in the past few years due to its minimally invasive nature, which does not require puncture of the brain. As neurosurgeons, we have the responsibility to select and perform appropriate surgical treatment based on sufficient knowledge of tremor to yield beneficial results in patients.