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Introduction: Central post-stroke pain (CPSP) is a common type of central neuropathic pain (CNeP) that can occur following the onset of stroke. The oral gabapentinoid mirogabalin besylate (mirogabalin) is a selective α2δ ligand that is effective for the treatment of CNeP, including CPSP. However, it is unknown whether the analgesic effect of mirogabalin on CPSP varies in patients with different background factors. Methods: This was a post hoc subgroup analysis of a multinational, open-label, long-term phase 3 study of mirogabalin for the treatment of CNeP conducted between March 2019 and December 2020. Data from patients with CPSP were stratified by type of stroke (ischemic or hemorrhagic), stroke location (thalamus, putamen, brainstem, or other), presence/absence of motor weakness, median time since stroke (≥ 59 or < 59 months), and median duration of CPSP (≥ 55.5 or < 55.5 months). Efficacy was assessed with the short-form McGill Pain Questionnaire (SF-MPQ), and treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were recorded. Results: This subanalysis included all 94 patients with CPSP from the phase 3 study; all were Japanese, and the mean age was 65.3 years. The least squares mean change [95% confidence interval] in SF-MPQ visual analog scale (VAS) score from baseline at week 52 (last observation carried forward) was − 17.0 [− 22.1, − 11.9] mm. Among the subgroups, least squares mean changes in SF-MPQ VAS scores were not different. Most TEAEs were mild or moderate; severe TEAEs occurred in six patients (6.4%). Somnolence (25.5%), peripheral edema (13.8%), dizziness (11.7%), and weight gain (6.4%) were the most common ADRs, and the types and frequencies of ADRs were similar among subgroups. Conclusion: Mirogabalin was generally effective and well tolerated in patients with CPSP, regardless of background factors such as stroke type or location, presence/absence of motor weakness, time since stroke, and duration of CPSP. Trial Registration: Trial registration number NCT03901352. [ABSTRACT FROM AUTHOR]

Central poststroke pain (CPSP) is one of the most under-recognized consequences of stroke, occurring in up to 10% of patients, and is also one of the most difficult to treat. The condition characteristically develops after selective lesions to the spinothalamic system, most often to the ventral posterior thalamus. Here, we suggest that CPSP is best characterized as a disorder of brain network reorganization, and that this characterization offers insight into the inadequacy of most current pharmacological treatments. Accordingly, we review the progress in identification of nonpharmacological treatments, which could ultimately lead to mechanism-based therapeutics. Of the invasive neurostimulation treatments available, electrical motor cortex stimulation seems to be superior to deep brain stimulation of the thalamus or brainstem, but enthusiasm for clinical use of the procedure is limited by its invasiveness. The current preference is for noninvasive transcranial magnetic stimulation, which, though effective, requires repeated application, causing logistical difficulties. Although CPSP is often severe and remains difficult to treat, future characterization of the precise underlying neurophysiological mechanisms, together with technological innovation, should allow new treatments to evolve. [ABSTRACT FROM AUTHOR]

Central poststroke pain (CPSP) is one of the most under-recognized consequences of stroke, occurring in up to 10% of patients, and is also one of the most difficult to treat. The condition characteristically develops after selective lesions to the spinothalamic system, most often to the ventral posterior thalamus. Here, we suggest that CPSP is best characterized as a disorder of brain network reorganization, and that this characterization offers insight into the inadequacy of most current pharmacological treatments. Accordingly, we review the progress in identification of nonpharmacological treatments, which could ultimately lead to mechanism-based therapeutics. Of the invasive neurostimulation treatments available, electrical motor cortex stimulation seems to be superior to deep brain stimulation of the thalamus or brainstem, but enthusiasm for clinical use of the procedure is limited by its invasiveness. The current preference is for noninvasive transcranial magnetic stimulation, which, though effective, requires repeated application, causing logistical difficulties. Although CPSP is often severe and remains difficult to treat, future characterization of the precise underlying neurophysiological mechanisms, together with technological innovation, should allow new treatments to evolve. [ABSTRACT FROM AUTHOR]

Abstract: Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation-guided 5Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ⩾30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P =.035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P =.035 and P =.019), and significantly increased after rTMS (P =.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP. [Copyright &y& Elsevier]

Abstract: There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5-Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow-up of 17days. The primary outcome was short-term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short-term change in the short form of the McGill pain questionnaire (SF-MPQ), cumulative changes in the following scores (VAS, SF-MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty-four NP patients were included in the intention-to-treat analysis. The real rTMS, compared with the sham, showed significant short-term improvements in VAS and SF-MPQ scores without a carry-over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients. [Copyright &y& Elsevier]

Summary: To investigate involvement of extrafocal regions in mesial temporal lobe epilepsy (MTLE), we retrospectively explored abnormalities in distribution of iomazenil (IMZ) activity by identifying interhemispheric asymmetry on IMZ-SPECT images of patients with MTLE. Fourteen MTLE patients in whom a good surgical outcome was achieved were included in the study. Voxel-based (VB) analysis and volume-of-interest (VOI) analysis with predefined VOIs were applied to compare IMZ binding between the hemispheres ipsilateral and contralateral to the epileptic focus. VB analysis showed significant decreases in iomazenil binding not only in the ipsilateral anterior temporal lobe including the mesial temporal structures but also in the ipsilateral extratemporal region including the insula, putamen, and medial occipital lobe. VOI analysis showed similar significant decreases in the ipsilateral parahippocampal gyrus, amygdala, putamen, lateral temporal lobe, and lateral occipital lobe. Results of the SPECT analyses suggest that decreased or dysfunctional IMZ activity extends from the mesial temporal lobe to the ipsilateral extrafocal region in patients with MTLE. [Copyright &y& Elsevier]

Abstract: Objective: To assess the pain-relieving effects of motor cortex electrical stimulation (MCS) within the central sulcus and the predictive factors retrospectively. Methods: Thirty-four patients with intractable neuropathic pain underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test electrodes were implanted within the central sulcus and on the precentral gyrus. Twelve patients received both MCS and repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex. Results: Pain reduction of ⩾50% was observed in 12 of 32 (36%) patients with ⩾12 months follow-ups (2 patients were excluded because of short follow-up). In 10 of the 12 patients who received test electrodes within the central sulcus and on the precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4 of these (40%) patients, positive effects were maintained at follow-ups. The pain reduction of rTMS significantly correlated with that of MCS during test stimulation. Conclusions: The test stimulation within the central sulcus was more effective than that of the precentral gyrus. In the selected patients, chronic stimulation within the central sulcus did not significantly improve long-term results. Significance: The present findings suggest that an intra-central sulcus is one of the favorable targets for MCS. [Copyright &y& Elsevier]

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Dose the low-frequency cerebellar rTMS affect the postural control and motor learning? • Cerebellar rTMS did not affect the body sway during upright standing. • Cerebellar rTMS did not change the sensory contribution for upright standing. • Cerebellar rTMS disrupted the motor learning of visually guided 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Low-frequency, bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson's disease (PD), but it is not particularly effective for segmental symptoms. Methods The optimal contacts for low-frequency (60 Hz) and high-frequency (130 Hz) single monopolar stimulation were determined. Then, in a randomized, double-blind, prospective crossover manner, 60-Hz and 130-Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD. Results The optimal contacts for 60-Hz stimulation were situated more ventrally than those for 130-Hz stimulation ( P = 0.038). Under the respective optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson's Disease Rating Scale motor score ( P < 0.001) and the akinesia ( P = 0.011) and axial motor signs ( P = 0.012) subscores without compromising the therapeutic effect on tremor and rigidity. Conclusions Low-frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Patients with Parkinson’s disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P <.001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P <.02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P <.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities. Quantitative evaluation on the effect of deep brain stimulation of the subthalamic nucleus on temperature sensation and pain suggested that it could improve impaired temperature sensation in patients with Parkinson’s disease. [Copyright &y& Elsevier]

Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurological disorder characterised by motor and non-motor deficits. Repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex at a high frequency (5 Hz or higher) is reported to be a potential treatment of PD. We aimed to assess the effect of rTMS on eye movement control in patients with PD in their 'on' state. We enrolled 14 patients with PD and assessed motor symptoms (Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale; MDS-UPDRS) and eye movement performances (visually guided saccades, volitional anti-saccades, and small involuntary saccades during fixation) at baseline and after administering bilateral 10 Hz rTMS on leg region of the motor cortex. We confirmed that rTMS improved the MDS-UPDRS motor scores and found that rTMS improved the anti-saccade success rate, which requires adequate inhibition of the reflexive response. The improvement in anti-saccade success rate was correlated with that of the postural instability gait difficulty (PIGD) sub-scores of MDS-UPDRS and lower baseline Japanese version of the Montreal Cognitive Assessment scores. This result is consistent with previous findings that PIGD and inhibitory control deficits share common brain dysfunctions in PD. rTMS may alleviate dysfunctions of that circuit and have a clinical effect. [ABSTRACT FROM AUTHOR]

We conducted a multicenter, randomized, patient- and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain (NP). Patients were randomly assigned to receive 5 daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving 4 weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. One hundred forty-four patients were assigned to the active or sham stimulation groups. The primary outcome, mean visual analogue scale decreases, was not significantly different (P = 0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between 2 groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (P < 0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various NP. Long-term administration to the responders should be investigated for the clinical use of rTMS on NP in the future trials. [ABSTRACT FROM AUTHOR]

To investigate whether gaze stabilization exercises (GSEs) improve eye and head movements and whether low-frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) inhibits GSE trainability. 25 healthy adults (real rTMS, n = 12; sham rTMS, n = 13) were recruited. Real or sham rTMS was performed for 15 min (1 Hz, 900 stimulations). The center of the butterfly coil was set 1 cm below the inion in the real rTMS. Following stimulation, 10 trials of 1 min of a GSE were conducted at 1 min intervals. In the GSE, the subjects were instructed to stand upright and horizontally rotate their heads according to a beeping sound corresponding to 2 Hz and with a gaze point ahead of them. Electrooculograms were used to estimate the horizontal gaze direction of the right eye, and gyroscopic measurements were performed to estimate the horizontal head angular velocity during the GSE trials. The percentage change from the first trial of motion range of the eye and head was calculated for each measurement. The percent change of the eye/head range ratio was calculated to assess the synchronous changes of the eye and head movements as the exercise increased. Bayesian two-way analysis of variance showed that cerebellar rTMS affected the eye motion range and eye/head range ratio. A post hoc comparison (Bayesian t-test) showed evidence that the eye motion range and eye/head range ratio were reduced in the fifth, sixth, and seventh trials compared with the first trial sham stimulation condition. GSEs can modulate eye movements with respect to head movements, and the cerebellum may be associated with eye–head coordination trainability for dynamic gazing during head movements. [ABSTRACT FROM AUTHOR]

Introduction Changes in motor symptoms and mood resulting from repetitive transcranial magnetic stimulation (rTMS) in patients with Parkinson’s disease (PD) have been addressed. However, the best area of the brain to target for stimulation has been still unknown. Since oculomotor behavior suggests a common mechanism underlying a general deficit in the motor control, recording of eye movement might offer a new quantitative evaluation of PD pathophysiology. Methods We assessed the effects of high-frequency rTMS (HF-rTMS) on motor and mood disturbances in patients with PD to identify the best target for treatment in the primary motor area (M1), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex (DLPFC). This randomized, double-blind crossover-design study examined 19 patients and investigated the efficacy of 3 consecutive days of HF-rTMS over the M1, SMA, and DLPFC. The results of rTMS at each location were compared to sham stimulation. We used several motor and/or non-motor scales to evaluate the Parkinsonian symptoms. Next, we enrolled 7 patients in order to learn how the performance of volitional saccade tasks and fixational eye movements were affected by HF-rTMS. We investigated bilateral 5 Hz rTMS over the M1 and assessed eye movement, which was recorded binocularly using a fast video-based eye tracker (the temporal and spatial resolutions were 500 Hz and 0.01°). Results The changes in the scores of the Unified Parkinson’s Disease Rating Scale part III (UPDRS–III) following the application of HF-rTMS over the M1 and SMA were significantly greater than those following sham stimulation. However, after the application of HF-rTMS over the DLPFC, the UPDRS–III scores were similar to those following sham stimulation. No significant improvements in mood disturbances were demonstrated. In the eye-movement study, the change of response time in anti-saccade performance improved significantly in patients with PD after applying HF-rTMS over the M1. The change of performance of saccade and frequency of fixational saccades for anti-saccade task which required reflex suppression showed a strong correlation with the posture and walk symptoms in PD. Conclusion The application of HF-rTMS to M1 and SMA significantly improved motor symptoms in patients with PD but did not affect mood disturbances. The volitional saccade performance may possibly reflect the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short- Form Mc Gill Pain Questionnaire 2 ( SF- MPQ-2- J). Design This is a cross-sectional study. Patients and Methods The original SF- MPQ-2 was translated into Japanese to create the SF- MPQ-2- J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF- MPQ-2- J was assessed using internal consistency, reliability coefficients ( Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF- MPQ-2- J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis ( CFA) was also performed to test the theoretical structure of the SF- MPQ-2- J. Results The internal consistencies calculated included continuous pain, α = 0.893; intermittent pain, α = 0.875; predominantly neuropathic pain, α = 0.917; affective descriptors, α = 0.857; and total score, α = 0.907. The reproducibility coefficients calculated included continuous pain, ρ = 0.81; intermittent pain, ρ = 0.78; predominantly neuropathic pain, ρ = 0.85; affective descriptors, ρ = 0.75; and total score, ρ = 0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. Conclusion These findings suggest that the reliability and validity of the SF- MPQ-2- J are excellent, and the SF- MPQ-2- J represents a cross-cultural equivalent to SF- MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain. [ABSTRACT FROM AUTHOR]

Patients with Parkinson's disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P<.001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P<.02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P<.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities. [ABSTRACT FROM AUTHOR]

Abstract: Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H2 15O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H2 15O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1±25.2 before SCS to 40.6±4.5 after SCS (mean±SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS. [Copyright &y& Elsevier]

Summary: Epileptic activities are known to be modulated by cortical excitability, which is altered with normal brain functioning such as movement. However, the relationship between the epileptic activity and movement has not been well studied. Here, we investigated movement-induced modulation of interictal spikes to reveal the relationship between epileptic activity and the movement-induced modulation of cortical activity. Two patients (three cases) with focal cortical dysplasia (FCD) of the pre- and/or post-central gyrus performed voluntary movements of their hands or mouths. During the movement, the interictal spikes of the sensorimotor cortex, which were measured by electrocorticograms (ECoG), were significantly reduced. This reduction strongly correlated with the event-related desynchronization (ERD) of the cortical oscillatory activity at the lower frequency bands (<25Hz) during movement. The epileptic activity was suggested to be modulated by the movement, which correlates with the ERD of the cortical oscillatory activity. [Copyright &y& Elsevier]

Abstract: Central post-stroke pain (CPSP) is one of the most common types of intractable pain. We reported that repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex relieves pain for patients who were refractory to medical treatment. But the mechanism is unclear. In the present study, we investigated relations between the characteristics of CPSP and the results of fiber tracking, which is the only noninvasive method of evaluating the anatomical connectivity of white matter pathways. Fiber tracking of the corticospinal tract (CST) and thalamocortical tract (TCT) was investigated in 17 patients with CPSP. The stroke lesion was located in a supratentorial region in all cases (corona radiata, one case; thalamus, seven cases; putamen, nine cases). Relations between the delineation ratio (defined as the ratio of the cross section of the affected side to that of the unaffected side) of the CST and of the TCT, manual muscle test score, pain score, region of pain, and efficacy of rTMS were evaluated. Fiber tracking was successful in 13 patients with the stroke lesion involving the TCT. The rTMS-effective group had higher delineation ratio of the CST (p =0.02) and the TCT (p =0.005) than the rTMS-ineffective group. Previous studies suggested that an intact CST allows pain control but did not discuss the TCT. Our results suggest that the TCT also plays a role in pain reduction by rTMS of the primary motor cortex and that the efficacy of rTMS for patients with CPSP is predictable by fiber tracking. [Copyright &y& Elsevier]

Objective The aim of this study was to investigate the incidence of and risk factors for postoperative delirium (POD) after deep brain stimulation (DBS) surgery in patients with Parkinson disease. Methods We analyzed the preoperative T1-weighted magnetic resonance imaging data of 71 patients with Parkinson disease who underwent DBS surgery. Multiple regression analysis was performed with age, l -dopa equivalent daily dose, laterality of the surgery, target regions, number of electrode trajectories tried, gray matter volume, and white matter (WM) volume as explanatory variables and the duration (number of days) of POD as the response variable. In addition, regional brain atrophy associated with POD was investigated by means of voxel-based morphometry. Results Excluding patients with outliers, 61 patients were included in the analyses. POD had occurred in 26 of the 61 patients (42.6%). Age and total WM volume were shown by multiple regression analysis to correlate significantly with the duration of POD ( P < 0.05 and < 0.01, respectively). WM was significantly reduced in the temporal stem, and the reduction in volume correlated significantly with the duration of POD ( P < 0.001). Gray matter atrophy was not associated with POD. Conclusions We found that age and WM atrophy in the temporal stem are factors predictive of POD after DBS surgery. In aged patients with temporal stem atrophy, surgical procedures and postoperative management should be carefully explored to reduce the risk of postoperative delirium. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the significance of difference between continuous and paroxysmal patterns of pain in the assessment of pain after brachial plexus injury.