Efficacy and safety of magnetic resonance-guided focused ultrasound treatment for refractory chronic pain of medial knee osteoarthritis.

OBJECTIVE: To elucidate the efficacy and safety of MRgFUS in the treatment for refractory pain derived from medial knee OA. METHODS: Twenty patients with medial knee OA eligible for total knee arthroplasty were included in this prospective, non-controlled study (UMIN000010193). MRgFUS treatment was provided at the site of most severe tenderness around the medial femorotibial joint of each patient under real-time monitoring of temperature. The goal temperature of the targeted bone surface was 55 °C. Numerical rating scale (NRS) worst pain scores, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores, EuroQol 5 dimensions index (EQ-5D) scores and pressure pain threshold (PPT) were evaluated before treatment (baseline) and at 1 week and 1, 3, 6, and 12 months post-treatment, respectively. Complications and adverse events were also assessed clinically and radiographically. RESULTS: Treatment response (a 50% or greater decrease in NRS score) was seen in 14 patients (14/19, 73.7%) at 12 months post-treatment. Mean NRS score rapidly decreased at 1 month after treatment and continued to decline through the following 12 months. At final follow-up, mean NRS score was 3.2 ± 1.9, significantly lower than at baseline (p = 0.0013). Mean WOMAC and EQ-5D scores also improved significantly from 1 month after treatment. Fifteen patients showed significant sustained increases in PPTs at the sites of most severe tenderness. No serious adverse events were observed during and after treatment. CONCLUSIONS: MRgFUS treatments were effective not only for managing refractory pain, but also for improving physical functions without adverse events in elderly patients with medial knee OA.

Effects of MRgFUS Treatment on Musculoskeletal Pain: Comparison between Bone Metastasis and Chronic Knee/Lumbar Osteoarthritis.

Local bone denervation by magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool for alleviation of pain in patients with painful bone metastasis (BM). Considering the underlying mechanism of pain alleviation, MRgFUS might be effective for various bone and joint diseases associated with local tenderness. This study was conducted to clarify the therapeutic effect of focused ultrasound in patients with various painful bone and joint diseases that are associated with local tenderness. Ten patients with BM, 11 patients with lumbar facet joint osteoarthritis (L-OA), and 19 patients with knee osteoarthritis (K-OA) were included. MRgFUS treatment was applied to the bone surface with real-time temperature monitoring at the target sites. Pain intensity was assessed using a 100 mm numerical rating scale (NRS) at various time points. Pressure pain threshold (PPT) was evaluated on the sonication area and control sites. Compared to baseline, the pain NRS scores significantly decreased in all groups 1 month after treatment, and PPT at the treated sites significantly increased in all groups 3 months after treatment. The percentage of patients who showed a ≥ 50% decrease in pain NRS scores at 1 month after treatment was 80% in BM, 64% in L-OA, and 78% in K-OA groups. PPTs were significantly higher after treatment at all evaluation time points. This study indicated that MRgFUS is effective in reducing pressure pain at the site of most severe tenderness in patients with painful bone and joint diseases. Treatment response was comparable between patients with BM, L-OA, and K-OA.

Discrepancy between functional recovery and cutaneous silent period change in surgically treated degenerative cervical myelopathy: a prospective pilot study.

STUDY DESIGN: Exploratory research OBJECTIVES: Cutaneous silent periods (CSPs) that reflect the inhibitory spinal cord reflex, can sensitively detect spinal cord dysfunction, and contribute to the diagnosis of degenerative cervical myelopathy (DCM). However, CSP changes after DCM surgery related to functional improvement have not been reported. SETTING: University hospital in Nankoku, Japan METHODS: CSP recorded at four time points-before surgery, 3, 6, 12 months after surgery-were investigated in 31 hands of 16 DCM patients. CSPs were categorized as follows: normal, delayed onset latency, shortened duration, onset delay with shortened duration, and absent CSP. Myelopathic symptoms were evaluated by the Japanese Orthopaedic Association score (JOA score). RESULTS: Normal CSPs were observed in five hands (16%) before surgery and six hands (19%) twelve months after surgery (P > 0.05). Either onset delay or shortened duration or both were observed in 18 hands (58%) before surgery and 16 hands (52%) twelve months after surgery (P > 0.05). Absent CSPs were observed in eight hands (26%) before surgery and nine hands (29%) twelve months after surgery (P > 0.05). Measured values of onset latency and duration also did not change throughout the study period (P > 0.05). On the other hand, JOA scores improved after surgery. (P = 0.003). CONCLUSIONS: CSP abnormalities persisted after surgery in most cases, indicating irreversible damage of the intramedullary reflex circuit. JOA score recovery without CSP recovery provides insight into postoperative neural recovery in DCM.

The Effect of Guidance regarding Home Exercise and ADL on Adolescent Females Suffering from Adverse Effects after HPV Vaccination in Japanese Multidisciplinary Pain Centers.

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

Short and long-term effects of exergaming for the elderly.

OBJECTIVE: Exergaming has been introduced in safe and beneficial intervention for the elderly. However, no study has examined exergaming-based interventions for the elderly that last several years. Therefore, we investigated the effectiveness and safety of a 12-week intervention using step training with exergaming for the elderly (12-week study). Moreover, we conducted an exergaming-based intervention for 3 years (3-year study). MATERIALS AND METHODS: 12-week study: Forty-two elderly persons participated in this study. Using an in-house developed exergaming protocol, a step training was performed for 15 min/session twice a week for 12 weeks. We investigated post-intervention changes in motor functions, successful step-rate, the intensity of exercise, which was evaluated using Borg scale (Rating of Perceived Exertion). 3-year study: An intervention using exergaming was conducted for 12 weeks by 20 elderly participants. Two courses/year of exercise were performed at 3-month intervals. This was continued for 3 years. The exercise continuation rate, its influence on motor functions were investigated. RESULTS: 12-week study: Lower-limb muscle strength, balancing capacity, and whole body reaction time significantly improved in the exercise group. The mean score on Borg scale was 12 ± 2 on the first day of the step exercise and 9 ± 2 on the final day. 3-year study: Exercise was continued in 16 out of the 20 subjects. The Timed Up and Go Test, duration of one-footed standing, and quadriceps strength significantly improved. CONCLUSION: The results of the present study showed that exergaming provided an appropriate exercise intensity for the elderly and safely improved motor functions. The exercise continuation rate in the 3-year study was high. Improvements in motor functions may contribute to the prevention of falls.

A Delayed Postoperative C5 Palsy due to Spinal Cord Lesion: A Typical Clinical Presentation but Unusual Imaging Findings.

Postoperative C5 palsy (C5 palsy) is a troublesome complication after cervical spine surgery and its etiology is still unclear. We experienced a case of C5 palsy after anterior decompression with fusion for cervical ossification of posterior longitudinal ligament with the typical clinical presentation of left deltoid and bicep weakness and left-arm pain without deterioration of myelopathy symptoms, albeit with the unusual imaging findings not shown preoperatively of a swelling in the spinal cord, and intramedullary high intensity change on T2-weighed MRI. The additional posterior surgery was carried out to decompress the swollen spinal cord. The abnormal findings disappear on MRI taken three weeks following the second surgery and the weakness improved fully within three months after the second surgery. This case report highlights the possibility of spinal cord lesion due to circulatory impairment as a cause of C5 palsy.

MR-guided focused ultrasound for the novel and innovative management of osteoarthritic knee pain.

BACKGROUND: Severe knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy. METHODS: Eight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment. RESULTS: Six patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p < 0.0001). There were no adverse side effects or complications during and after treatment. CONCLUSIONS: These initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA. TRIAL REGISTRATION: Trial Registration: UMIN000010193.

Health survey of numbness/pain and its associated factors in Kotohira, Japan.

We conducted a survey of adults in Kotohira, a town of about 10,000 people located in the Nakatado District of Kagawa Prefecture, Japan. The survey was distributed to 8184 individuals, and effective responses were received from 3863 persons (response rate, 47.2%) during the survey period. Results regarding numbness and pain showed numbness alone in 7.7%, pain alone in 7.2%, both numbness and pain in 6.0%, and neither numbness nor pain in 79.6%. Spine and spinal cord damage was reported present by 5.4%, and absent by 94.6%. Analysis using the Short-Form Health Survey questionnaire, with comparison between subjects reporting both numbness and pain in the extremities and subjects with either numbness or pain alone, showed lower scores for in Short-Form Health Survey subscales (physical functioning, role [physical, emotional], bodily pain, vitality, and mental health). Subjects with numbness alone generally reported no disability in daily life. In a secondary survey, analysis of neurological findings by specialists identified 6 cases of "pain following spinal cord damage" in which spinal cord-related pain developed in the hands or feet. This represented 0.15% of the survey population starting from the primary survey.

Changes in calcitonin gene-related peptide expression following joint immobilization in rats.

Long-term immobilization by casting can occasionally cause pathologic pain states in the immobilized side. The underlying neurophysiological mechanisms of immobilization-related pain are not well understood. For this reason, we specifically examined changes of calcitonin gene-related peptide (CGRP) expression in the dorsal root ganglion (DRG), spinal dorsal horn and posterior nuclei (cuneate nuclei) in a long-term immobilization model following casting for 5 weeks. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90 degrees of flexion. In this model, CGRP in immobilized (ipsilateral) side was distributed in larger DRG neurons compared with contralateral side, even though the number of CGRP-immunoreactive (CGRP-IR) neurons did not differ. Spinal laminae III-V, not laminae I-II in ipsilateral side showed significantly high CGRP expression relative to contralateral side. CGRP expression in cuneate nuclei was not significantly different between ipsilateral and contralateral sides. Long-term immobilization by casting may induce phenotypic changes in CGRP expression both in DRG and spinal deep layers, and these changes are partly responsible for pathological pain states in immobilized side.

An intramedullary free vascularized fibular graft combined with pasteurized autologous bone graft in leg reconstruction for patients with osteosarcoma.

The use of pasteurized autologous bone graft has been an innovation in limb-salvage surgery; however, its principal disadvantage is fracture, infection, pseudoarthrosis, and bone resorption. We present two cases in which an intramedullary free vascularized fibular graft combined with pasteurized autologous bone graft was performed for immediate femur or tibia reconstruction following osteosarcoma resection. The rationale of this method is to combine the mechanical strength of a pasteurized bone with the biological activity of a vascularized bone. The pasteurized bone graft provides bone stock and early stability and the addition of the vascularized bone graft substantially facilitates host-pasteurized bone union. This combination procedure may be a recommended option for reconstruction of the lower leg, preserving knee joint function for patients with osteosarcoma.

Anterolisthesis and retrolisthesis of the cervical spine in cervical spondylotic myelopathy in the elderly.

BACKGROUND: Degenerative spondylolisthesis of the cervical spine has received insufficient attention in contrast to that of the lumbar spine. The authors analyzed the functional significance of anterior and posterior degenerative spondylolisthesis (anterolisthesis and retrolisthesis) of the cervical spine to elucidate its role in the development of cervical spondylotic myelopathy (CSM) in the elderly. METHODS: A total of 79 patients aged 65 or older who eventually had surgical treatment for CSM were evaluated radiographically. RESULTS: Altogether, 24 patients (30%) had displacement of 3.5 mm or more (severe spondylolisthesis group), 31 had displacement of 2.0-3.4 mm (moderate spondylolisthesis group), and 24 had less than 2.0 mm displacement (mild spondylolisthesis group). The severe spondylolisthesis group consisted of 14 patients with anterolisthesis (anterolisthesis group) and 10 patients with retrolisthesis (retrolisthesis group). Patients with severe spondylolisthesis had a high incidence (93%) of degenerative spondylolisthesis at C3/4 or C4/5 and significantly greater cervical mobility than those with mild spondylolisthesis. The anterolisthesis group, but not the retrolisthesis group, had a significantly wider spinal canal than the mild spondylolisthesis group, although the degree of horizontal displacement and cervical mobility did not differ significantly between the anterolisthesis and retrolisthesis groups. Severe cord compression seen on T1-weighted magnetic resonance imaging (MRI) scans and high-intensity spinal cord signals seen on T2-weighted MRI scans corresponded significantly to the levels of the spondylolisthesis. CONCLUSIONS: Degenerative spondylolisthesis is not a rare radiographic finding in elderly patients with CSM, which tends to cause intense cord compression that is seen on MRI scans. Greater mobility of the upper cervical segments may be a compensatory reaction for advanced disc degeneration of the lower cervical segments, leading to the development of degenerative spondylolisthesis. With a similar degree of displacement, anterolisthesis tends to have a greater impact on the development of CSM than retrolisthesis.

Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to colorectal distention.

The purpose of this study was to examine the effect of cutaneous inflammation on the responses of viscerosomatic convergent dorsal horn neurons to graded colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous inflammation induced by intradermal injection of capsaicin in the receptive field (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the RF induced an increase in the spontaneous activity of dorsal horn neurons, an expansion in the size of their RF and facilitated their responses to cutaneous stimuli. An injection placed in the center of the RF attenuated the responses to noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in the responses to CRD but not to cutaneous stimuli. These results indicate that the inhibitory effects, evoked by cutaneous inflammation, can modulate the responses of dorsal horn neurons to CRD, independent of its effect on the responses to cutaneous mechanical stimuli.

Functional importance of degenerative spondylolisthesis in cervical spondylotic myelopathy in the elderly.

STUDY DESIGN: A correlation was studied between degenerative spondylolisthesis (DSL) of the cervical spine and spinal-evoked potentials intraoperatively recorded in elderly patients who had surgical treatment for cervical spondylotic myelopathy. OBJECTIVE: To investigate the functional importance of cervical DSL in elderly patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Cervical DSL has received insufficient attention in contrast to the lumbar DSL. The authors are unaware of any journal article in which this condition has been evaluated electrophysiologically. METHODS: This study investigated 47 patients with 68 DSL of 2 mm or more (3.1 +/- 0.9 mm; range, 2-6 mm) who underwent serial intervertebral recording of spinal-evoked potentials from either the intervertebral disc or the ligamentum flavum after epidural stimulation. RESULTS: All the study patients had unequivocal evidence of a focal conduction block, with the area of negative evoked potential peak reduced to less than 60% that of the immediately caudal level: 31 at C3-C4, 12 at C4-C5, and 1 each at C1-C2, C2-C3, C5-C6, and C6-C7. The site of conduction block matched the level of DSL in 30 patients, but not in 17 patients. The DSL accompanied by conduction block had significantly greater displacement with greater angular mobility than that without conduction block. CONCLUSIONS: A significant association between DSL and conduction block in the face of a relatively wide canal indicates the functional importance of DSL in elderly patients with cervical spondylotic myelopathy. In this age group, a high incidence of both DSL (81%) and focal conduction block (91%) at the upper cervical level (C3-C4 or C4-C5) is of clinical interest.

Analgesic effects of ketamine ointment in patients with complex regional pain syndrome type 1.

OBJECTIVE: Ketamine hydrochloride (KET), an agent used for general anesthesia, has local anesthetic effects and N-methyl-D-aspartate (NMDA) receptor antagonist action. Because recent studies emphasized the role of peripherally distributed NMDA receptors in processing the nociceptive information, we investigated whether peripheral application of the ointment containing KET is able to attenuate the symptoms of local neuropathic pain. CASE REPORTS: We applied ointment containing KET (0.25%-1.5%) to the affected area on limbs in 5 patients with complex regional pain syndrome type I (CRPS I) and in 2 patients with type II (CRPS II). One to 2 weeks later, we observed improvement of the report of pain intensity, measured by the visual analog scale, in 4 patients with acute early dystrophic stage of CRPS I. Swelling of the affected limbs subsided as well. No apparent changes were noticed in 1 patient with chronic atrophic stage of CRPS I and in both patients with CRPS II. CONCLUSION: Topical application of KET appears to be beneficial for the patients with acute early dystrophic stage of CRPS I because of either its local anesthetic effect or NMDA receptor antagonist action. Patients with chronic atrophic stage of CRPS I and CRPS II patients do not appear to respond to this treatment.

Changes of wide dynamic range neuronal responses to mechanical cutaneous stimuli following acute compression of the rat sciatic nerve.

To investigate the changes in central neuronal activity in response to cutaneous stimulation following acute nerve compression, the responses of wide dynamic range dorsal horn neurons (n = 13) to graded mechanical cutaneous stimuli (brush, press, pinch, and squeeze) were recorded in anesthetized male Sprague-Dawley rats before and during compression, and after the release of the compression. A small vascular clip (pinching force, 120 g) was applied to compress the sciatic nerve for 30 min. In 12 neurons, background activities increased transiently for 1.5 to 4 min after nerve compression. Similarly, after the release of the compression, 7 neurons showed a transient increase in background activities. The responses to brush, press, and pinch were inhibited significantly 10 min after the nerve compression. The responses to press and pinch recovered gradually after the release of the compression. Responses to squeeze were little affected throughout the experimental period. Acute compression of the rat sciatic nerve can cause short periods of continuous increased spontaneous firing and can attenuate the dorsal horn neuronal responses to cutaneous stimuli. In particular, the neuronal responses to innocuous stimuli were more susceptible to compression of the nerve than the responses to noxious stimuli.