Koichi Hosomi

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

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.

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial.

&NA; The double‐blinded randomized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events. &NA; 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 17 days. 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.

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.

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O 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.

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

&NA; 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.

Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

&NA; Repetitive transcranial magnetic stimulation of the primary motor cortex restored the abnormal intracortical facilitation in patients with central poststroke pain. &NA; 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 5 Hz 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.

Modulating the pain network—neurostimulation for central poststroke pain

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.

Differential Efficacy of Electric Motor Cortex Stimulation and Lesioning of the Dorsal Root Entry Zone for Continuous vs Paroxysmal Pain After Brachial Plexus Avulsion

BACKGROUND:Pain after traumatic brachial plexus avulsion (BPA) has 2 distinct patterns: continuous burning pain and paroxysmal shooting pain. Lesioning of the dorsal root entry zone (DREZotomy) is more effective for paroxysmal than continuous pain. It is unknown, however, whether electric motor cortex stimulation (EMCS) has a differential effect on continuous vs paroxysmal BPA pain. OBJECTIVE:To analyze the differential effect of EMCS and DREZotomy on continuous vs paroxysmal BPA pain in a series of 15 patients. METHODS:Fifteen patients with intractable BPA pain underwent DREZotomy alone (n = 7), EMCS alone (n = 4), or both procedures (n = 4). Pain intensity was evaluated with the Visual Analog Scale, and separate ratings were recorded for paroxysmal and continuous pain. Pain relief was categorized as excellent (> 75% pain relief), good (50%-75%), or poor (< 50%). Favorable outcome was defined as good or better pain relief. RESULTS:Eight patients had EMCS; 7 were followed up for an average of 47 months. Of those 7 patients, 3 (42%) with continuous pain had favorable outcomes compared with no patients with paroxysmal pain. Eleven patients had DREZotomy; 10 were followed up for an average of 31 months. Of those 10 patients, 7 (70%) with paroxysmal pain had favorable outcomes compared with 2 (20%) with continuous pain. CONCLUSION:EMCS was ineffective for paroxysmal pain but moderately effective for continuous pain. DREZotomy was highly effective for paroxysmal pain but moderately effective for continuous pain. It may be prudent to use EMCS for residual continuous pain after DREZotomy.

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 (≥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.