稲毛 一秀

[This corrects the article on p. 338 in vol. 9, PMID: 26097648.].

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-caused pyogenic spondylitis is a serious complication associated with lumbar fusion surgery. Often, anti-MRSA drugs are not used properly or patients discontinue drug use because of side effects including renal failure. CASE PRESENTATION: We report a case at our hospital of a 54-year-old male renal-transplant patient who developed MRSA vertebral osteomyelitis after spinal fusion and was treated effectively with linezolid. After diagnosis of post-fusion surgery osteomyelitis, we conducted emergency flushing and debridement and began linezolid treatment (1200 mg/day, divided) immediately after the surgery. The level of C-reactive protein gradually decreased and became negative 4 weeks after the initiation of linezolid treatment. Serum creatinine level was approximately 1.3 mg/dL throughout the treatment period, indicating no deterioration in renal function. CONCLUSION: These results suggest that early flushing and debridement together with linezolid administration is an effective treatment for MRSA vertebral osteomyelitis in renal-transplant patients.

Recently several authors have reported that diffusion tensor imaging (DTI) might provide a new understanding of sciatica. The purpose of this study was to investigate the clinical feasibility of DTI for the evaluation of lumbar spinal nerve of patients with sciatica associated with lumbar degenerative disorders. Thirty-four patients (25men, mean age63. 3years) with degenerated lumbar disease, 14 patients with lumbar spinal stenosis with foraminal stenosis, 12 with lumbar spinal stenosis without foraminal stenosis, five with lumbar disc herniation, two with discogenic low back pain, and one with spondylolysis who underwent 3.0T magnetic resonance (MR) imaging and surgical treatment were included in the present study. Fractional anisotropy (FA) was calculated from an FA map, and tractography was investigated. In asymptomatic nerves, tractography showed all L3-S1 spinal nerve roots clearly. Abnormalities of tractography were classified into three types by shape; "Disrupted", "Narrowing", and "Tapering". More abnormalities of tractography were found in patients with lumbar spinal stenosis, and especially in patients with foraminal stenosis. The disrupted type was the most common. The mean FA of entrapped symptomatic nerves was less than seen on the intact side. This study demonstrates that tractography shows abnormal findings for nerve roots in lumbar spinal degeneration and that FA decreases in symptomatic roots. DTI may offer not only morphological evaluation, but also quantitative evaluation. We believe that DTI can be used as a tool for the diagnosis of lumbar spinal degenerative disease.

The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain-related mediators, such as interleukin-6 (IL-6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL-6 and IL-6 receptor (IL-6R) expression after IVD injury as well as determine the involvement of IL-6/IL-6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL-6 and IL-6R in IVDs by enzyme-linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL-6 inhibitor by evaluating pain-related protein, calcitonin gene-related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL-6 and IL-6R. IL-6 and IL-6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL-6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL-6 and IL-6R expression levels are responsive to IVD injury and that inhibition of IL-6/IL-6R signaling may be a promising analgesic treatment for degenerative disc diseases.

椎間板性腰痛の病態と今後の展望について、1)innervation:感覚神経支配が存在すること、2)inflammation:その感覚神経を感作する因子が存在すること、3)hypermobility:不安定性があること、に分けて述べた。現時点では、術前の痛みや術後残存する痺れと術前拡散テンソル画像での障害の程度が相関しており、基礎、臨床的に認められた椎間板内への神経発芽を可視化することが現実化できると期待される。

PURPOSE: Nuclear factor-κB (NF-κB), receptor activator of NF-κB (RANK), and RANK ligand (RANKL) are transcriptional regulators of inflammatory cytokines. RANKL expression in dorsal root ganglion (DRG) neurons is elevated in animal models of pain or intervertebral disc herniation. We sought to evaluate the effect of anti-RANKL antibodies on sensory nerves innervating injured intervertebral discs. METHOD: We labeled DRG neurons innervating L5-6 discs with FluoroGold (FG). The L5-6 discs of 36 rats were punctured using a 23-gage needle and 18 rats underwent sham surgery without disc puncture. The puncture group was evenly subdivided into a group in which 10 μl saline was administered to the injured disc and a group in which 10 μl of anti-RANKL antibody was administered. Seven and 14 days postsurgery, DRGs at L2 level were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was determined. Amount of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was measured within the intervertebral discs in each group at 7 and 14 days after surgery using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The proportion of CGRP-IR DRG neurons to total FG-labeled neurons innervating injured intervertebral discs and amount of TNF-α and IL-6 in the injured discs in the saline control group was significantly increased compared with that found in rats from the sham surgery group (P < 0.05). However, application of anti-RANKL antibody to the injured discs significantly decreased the proportion of CGRP-IR DRG neurons to total FG-labeled neurons and amount of TNF-α and IL-6 in the injured discs (P < 0.05). CONCLUSIONS: TNF-α and IL-6 in the injured discs increased and CGRP expression increased in DRG neurons innervating injured discs, and antibodies to RANKL could suppress this increased TNF-α, IL-6, and CGRP expression. RANKL may be a therapeutic target for pain control in patients with lumbar disc degeneration.

PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-α (TNFα) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFα inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFα is one factor that induces OA pain.

STUDY DESIGN: Prospective case series. PURPOSE: To examine the clinical efficacy of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion (OLIF) for degenerated lumbar spinal kyphoscoliosis. OVERVIEW OF LITERATURE: The existing surgical procedures for the treatment of spinal kyphotic deformity, including Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection procedures, are invasive in nature. Extreme lateral interbody fusion to provide less invasive treatment of the deformity has been reported, but complications including spinal nerve and psoas muscle injury have been noted. In the current study, we examined the clinical efficacy and complications of OLIF for degenerated lumbar spinal kyphoscoliosis. METHODS: Twelve patients with degenerated lumbar spinal kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with open pedicle screws or percutaneous pedicle screws, without real-time monitoring by electromyography. Visual analog scale score and Oswestry disability index were evaluated before and 12 months after surgery, and fusion rate at OLIF cage, correction of the deformity, total blood loss, and surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery (p<0.05). Fusion rate was found to be 90%, balance parameters also improved after surgery (p<0.05), and average total blood loss was less than 350 mL. There was no spinal nerve, major vessel, peritoneal, or urinary injury, or breakage of instrumentation. CONCLUSIONS: OLIF surgery for degenerated lumbar spinal kyphoscoliosis is less invasive than other procedures and good surgical results were produced without major complications.

STUDY DESIGN: Retrospective case series. PURPOSE: To examine the most effective duration of teriparatide use for spinal fusion in women with postmenopausal osteoporosis. OVERVIEW OF LITERATURE: We reported that daily subcutaneous injection of teriparatide (parathyroid hormone) significantly improved bone union after instrumented lumbar posterolateral fusion (PLF) in women with postmenopausal osteoporosis when compared with oral administration of bisphosphonate. However, the most effective duration of teriparatide use for spinal fusion has not been explored. METHODS: Forty-five women with osteoporosis diagnosed with degenerative spondylolisthesis from one of the three treatment groups were evaluated based on: short-duration treatment (average, 5.5 months; n=15; daily subcutaneous injection of 20 µg teriparatide), long-duration treatment (average, 13.0 months; n=15; daily subcutaneous injection of 20 µg teriparatide), and bisphosphonate treatment (average, 13.0 months; n=15; weekly oral administration of 17.5 mg risedronate). All patients underwent PLF with a local bone graft. Fusion rate and duration of bone union were evaluated 1.5 years after surgery. RESULTS: Bone union rate and average duration for bone union were 92% and 7.5 months in the long-duration treatment group, 80% and 8.5 months in the short-duration treatment group, and 70% and 10.0 months in the bisphosphonate treatment group, respectively. Results of bone union rate and average duration for bone union in the teriparatide treatment groups were significantly superior to those in the bisphosphonate treatment group (p<0.05); whereas, significantly superior results were observed in long-duration treatment group when compared with short-duration treatment group (p<0.05). CONCLUSIONS: Daily injection of teriparatide for bone union was more effective than oral administration of bisphosphonate. Furthermore, a longer period of teriparatide treatment for bone union was more effective than a shorter period of same treatment.

This study aimed to evaluate the time course of local changes during the acute phase of gastrocnemius muscle strain, in a rat model, using an in vivo imaging system. Thirty-eight, 8-week-old Sprague-Dawley male rats were used in our study. Experimental injury of the right gastrocnemius muscle was achieved using the drop-mass method. After inducing muscle injury, a liposomally formulated indocyanine green derivative (LP-iDOPE, 7 mg/kg) was injected intraperitoneally. We evaluated the muscle injuries using in vivo imaging, histological examinations, and enzyme-linked immunosorbent assays. The fluorescence peaked approximately 18 h after the injury, and decreased thereafter. Histological examinations revealed that repair of the injured tissue occurred between 18 and 24 h after injury. Quantitative analyses for various cytokines demonstrated significant elevations of interleukin-6 and tumor necrosis factor-α at 3 and 18 h post-injury, respectively. The time course of fluorescence intensity, measured using in vivo imaging, demonstrated that the changes in cytokine levels and histopathologic characteristics were consistent. Specifically, these changes reached peaked 18 h post-injury, followed by trends toward recovery.

PURPOSE: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. MATERIALS AND METHODS: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. CONCLUSION: OLIF surgery produced good surgical results without any major complication.

An 80-year-old woman presented with severe thoracolumbar kyphosis due to spinal tuberculosis with chronic low back pain and gait disturbance. Radiographs showed T9-L1 bony union in the anterior and posterior longitudinal ligaments. Rigid bony union of the L2 and L3 vertebral bodies, with trapezoid-shaped deformity, a sagittal vertical axis (SVA) of approximately 570 mm, and a severe pelvic posterior inclination, were also evident. No residual tuberculous disease was detected. The patient was treated with kyphoplasty, which included an L2 pedicle subtraction vertebral osteotomy (PSO), and T9-S1 fixation. The procedure yielded a 45° correction in the sagittal alignment and enhanced local stability, resulting in an SVA of 50 mm. Her post-operative lower back pain and the gait disturbance resolved. The osteotomy site showed sufficient bony union 8 months post-operatively. PSO yielded marked improvements and stability with no complications such as pseudoarthritis at the osteotomy site. Also her sagittal alignment was corrected to achieve adequate stability with sufficient activities of daily living and improved quality of life. Vertebral osteotomy on those with rigid deformity gives good and stable clinical outcome.

拡散テンソル画像は水分子の拡散の異方性をとらえる撮像法で定量的MRIとして脊髄神経の可視化・定量評価に応用された。脊柱管、椎間板へ応用することにより、椎間孔狭窄など従来の画像診断では評価困難な病変の可視化や脊髄神経の定量評価のみならず、脊柱管の狭窄や椎間板の変性について3次元的かつ定量的な評価が可能であった。拡散テンソル画像は腰痛疾患における新たな画像診断ツールとしての有用性について示された。(著者抄録)

若齢期の脊椎カリエスによる腰椎高度後彎症例に起因する慢性腰痛および歩行障害をきたしていた80歳女性に対して,骨切り術を用いた矯正固定術を行った。術前画像検査にてT9-L1椎体は靱帯骨化による癒合と脊椎カリエスによるL2-3椎体の変形癒合に伴う矢状面アライメントの高度不整による後彎変形を呈していた。脊椎矢状面アライメントの評価パラメータであるLL(Lumbar Lordosis:腰椎前彎角。正常35〜50°程度)は-24.1°,SVA(sagittal vertical axis:第7頸椎の垂線から仙骨後壁上縁までの距離。正常50mm以下)は570mmと大きく偏移していた。本患者に対してL2椎体に対し椎弓根切除を特徴とする骨切り術式であるpedicle subtraction osteotomy(PSO)による矯正固定術を行った。椎体の骨切りとT9-S1固定術を併用することにより約56.1°の矯正角を獲得,矢状面アライメントはLL32°,SVA56mmと改善した。その結果腰痛や歩行障害などの症状は消失,独歩にて自宅退院となりADLおよびQOLは著明な改善をきたした。高齢化社会の進行に伴い変性による脊柱後側彎の症例は増加傾向にあるが,特に本症例のような脊椎カリエスに伴う高度脊柱変形を伴う症例では,生理的自然経過を超越した高度変形に伴う矢状面アライメントの異常がもたらす脊髄や神経根の圧迫・狭窄による痛みやしびれ,麻痺などの神経症状に加えて体幹筋のバランス異常・負荷増加による疼痛や歩行異常を来すことが多い。このような症例では脊柱の可動性も極度に低下しているため通常の固定術・除圧術では十分な矯正が得られないことが多く,本症例のようにPSOをはじめとした骨切り矯正固定術を併用した術式が有効である。(著者抄録)

STUDY DESIGN: Retrospective study. PURPOSE: We conducted a study to investigate the time course changes in bone metabolic markers after the administration of the anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody and to assess drug compliance among osteoporotic patients. OVERVIEW OF LITERATURE: The anti-RANKL antibody is expected to provide an improvement in those with a bone metabolism disorder. However there are only a few clinical reports available on the effect of treatment. METHODS: We included 40 post-menopausal osteoporotic patients who received the anti-RANKL antibody. To determine the time course changes in the bone metabolic markers, we measured the serum tartrate-resistant acid phosphatase 5b (TRACP 5b; a bone resorption marker) and the serum N-terminal propeptide of type 1 collagen (P1NP; a bone formation marker) levels prior to and 1 month after administrating the anti-RANKL antibody. To evaluable drug compliance, we assessed the dropout rate during treatment and at 6 months after treatment. RESULTS: The average TRACP 5b level significantly decreased from 574.8 mU/dL before treatment to 153.2 mU/dL 1 month after treatment (p<0.05). There was no significant difference in the average P1NP level, which was 56.9 µG/L and 35.1 µG/L before and 1 month after treatment, respectively (p>0.05). As for drug compliance, we did not have any dropouts during the treatment or after 6 months (dropout rate: 0%). CONCLUSIONS: Our study suggests that anti-RANKL antibody treatment suppresses bone resorption and maintains bone formation.

多血小板血漿(PRP)を用いた脊椎骨癒合促進について検討した。腰椎すべり症を伴う腰部脊柱管狭窄症39例を対象とし、インプラント+局所骨群(I群)、インプラント+局所骨+PRP群(II群)に分けた。PRPの血小板濃度は血液中の約8倍と有意に増加した。また、PRP中の骨形成に関与するPDGF-AA、AB、BB、TGF-βは血中濃度の50倍以上であった。骨癒合は全例で認め、骨癒合までの期間はI群9.8±0.53ヵ月、II群7.8±0.67ヵ月で、II群において有意に短縮した。VASによる疼痛評価は両群間で有意差はなかった。有害事象は、両群とも感染、発熱、臓器機能障害などはなかった。