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.

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.

Voluntary control of semantic neural representations by imagery with conflicting visual stimulation.

Neural representations of visual perception are affected by mental imagery and attention. Although attention is known to modulate neural representations, it is unknown how imagery changes neural representations when imagined and perceived images semantically conflict. We hypothesized that imagining an image would activate a neural representation during its perception even while watching a conflicting image. To test this hypothesis, we developed a closed-loop system to show images inferred from electrocorticograms using a visual semantic space. The successful control of the feedback images demonstrated that the semantic vector inferred from electrocorticograms became closer to the vector of the imagined category, even while watching images from different categories. Moreover, modulation of the inferred vectors by mental imagery depended asymmetrically on the perceived and imagined categories. Shared neural representation between mental imagery and perception was still activated by the imagery under semantically conflicting perceptions depending on the semantic category.

[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.

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.

Real-Time Neurofeedback to Modulate ß-Band Power in the Subthalamic Nucleus in Parkinson's Disease Patients.

The ß-band oscillation in the subthalamic nucleus (STN) is a therapeutic target for Parkinson's disease. Previous studies demonstrated that l-DOPA decreases the ß-band (13-30 Hz) oscillations with improvement of motor symptoms. However, it has not been elucidated whether patients with Parkinson's disease are able to control the ß-band oscillation voluntarily. Here, we hypothesized that neurofeedback training to control the ß-band power in the STN induces plastic changes in the STN of individuals with Parkinson's disease. We recorded the signals from STN deep-brain stimulation electrodes during operations to replace implantable pulse generators in eight human patients (3 male) with bilateral electrodes. Four patients were induced to decrease the ß-band power during the feedback training (down-training condition), whereas the other patients were induced to increase (up-training condition). All patients were blinded to their assigned condition. Adjacent contacts that showed the highest ß-band power were selected for the feedback. During the 10 min training, patients were shown a circle whose diameter was controlled by the ß-band power of the selected contacts. Powers in the ß-band during 5 min resting sessions recorded before and after the feedback were compared. In the down-training condition, the ß-band power of the selected contacts decreased significantly after feedback in all four patients (p < 0.05). In contrast, the ß-band power significantly increased after feedback in two of four patients in the up-training condition. Overall, the patients could voluntarily control the ß-band power in STN in the instructed direction (p < 0.05) through neurofeedback.

Spinal cord stimulation for central poststroke pain.

BACKGROUND: Although spinal cord stimulation (SCS) has been shown to be effective for treating neuropathic pain of peripheral origin, its effectiveness for central poststroke pain (CPSP) is not well established. OBJECTIVE: We report our experience with SCS in 30 consecutive patients with intractable CPSP. METHODS: All patients underwent a percutaneous SCS trial. When patients decided to proceed, they received a permanent SCS system. Pain intensity was evaluated by a visual analogue scale (VAS). The Patient Global Impression of Change (PGIC) scale was also assessed at the latest follow-up visit as an indicator of overall improvement. RESULTS: During trial stimulation, pain relief was good (> or =50% VAS score reduction) in 9 patients (30%), fair (30%-49% reduction) in 6 patients (20%), and poor (<30% reduction) in 15 patients (50%). Ten patients elected to receive a permanent SCS system. Nine of these 10 patients were followed long-term (mean, 28 months; range, 6-62 months). Seven patients reported significant pain relief on the VAS (5 = good and 2 = fair). On the PGIC scale, 6 of these 7 patients reported a rating of 2 (much improved) and 1 reported a rating of 3 (minimally improved). Of the remaining 2 patients, 1 reported a rating of 4 (no change) and 1 reported a rating of 5 (minimally worse). The median VAS score in the 9 patients decreased significantly from 8.6 (range, 6.0-10.0) to 4.5 (range, 3.0-8.0; P = .008). There were no significant reported complications. CONCLUSION: SCS may provide improved pain control in a group of patients with intractable CPSP and may have therapeutic potential for intractable CPSP.

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H(2)15O PET study.

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 H(2)(15)O 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 H(2)(15)O 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.

Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation.

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.

Outcome of bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease: correlation with intra-operative multi-unit recordings but not with the type of anaesthesia.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson's disease (PD). OBJECTIVE: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. METHODS: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson's Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. RESULTS: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. CONCLUSION: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

Electrical stimulation of primary motor cortex within the central sulcus for intractable neuropathic pain.

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 > or =50% was observed in 12 of 32 (36%) patients with > or =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.