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.

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.

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.

[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.

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.

Induced sensorimotor brain plasticity controls pain in phantom limb patients.

The cause of pain in a phantom limb after partial or complete deafferentation is an important problem. A popular but increasingly controversial theory is that it results from maladaptive reorganization of the sensorimotor cortex, suggesting that experimental induction of further reorganization should affect the pain, especially if it results in functional restoration. Here we use a brain-machine interface (BMI) based on real-time magnetoencephalography signals to reconstruct affected hand movements with a robotic hand. BMI training induces significant plasticity in the sensorimotor cortex, manifested as improved discriminability of movement information and enhanced prosthetic control. Contrary to our expectation that functional restoration would reduce pain, the BMI training with the phantom hand intensifies the pain. In contrast, BMI training designed to dissociate the prosthetic and phantom hands actually reduces pain. These results reveal a functional relevance between sensorimotor cortical plasticity and pain, and may provide a novel treatment with BMI 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.

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.